MXPA06008948A - Chemokine ccr5 receptor modulators - Google Patents

Abstract

This invention relates to piperidine derivatives of formulae (I) with substituents as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is implicated. More particularly, the present invention relates to 1-oxa-3,8-diaza-spiro[4.5]decan-2-one and 1-oxa-3,9-diaza-spiro[5.5]undecan-2-one compounds and related derivatives, to compositions containing and to uses of such derivatives. Disorders that may be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (and the resulting acquired immune deficiency syndrome, AIDS), diseases of the immune system and inflammatory diseases.

Description

MODULATORS OF THE CCR5 CHEMICAL RECEIVER DESCRIPTION OF THE INVENTION This invention relates to piperidine derivatives useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is involved. Particularly, the present invention relates to the compounds and derivatives related to 1-oxa-3, 8-diaza-spiro [4.5] decan-2-one and l-oxa-3, 9-diaza-spiro [5.5] ndecan- 2-one, to compositions that contain them and to the uses of such derivatives. Disorders that can be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (as well as the resulting acquired immunodeficiency syndrome, AIDS), diseases of the immune system and inflammatory diseases of the immune system. The compounds of the present invention modulate the activity of the chemokine receptors CCR5. Chemokines are a large family of pro-inflammatory peptides that exert their pharmacological effect through receptors coupled to protein G. The name "chemokine" is a contraction of "chemotactic cytokines". Chemokines are a family of leukocyte chemotactic proteins capable of attracting leukocytes to various tissues, which is an essential response to REF. : 174322 inflammation and infection. Human chemokines include approximately 50. small proteins of 50-120 amino acids that are structurally homologous. (M. Baggiolini et al., Annu. Rey, Immunol., 1997 15: 675-705). Modulators of the CCR5 receptor can be useful in the treatment of various inflammatory diseases and conditions and in the treatment of HIV-1 infection and genetically related retroviruses. As leukocytic chemoattractants, chemokines play an indispensable role in the attraction of leukocytes to various tissues of the body, a process that is essential both for inflammation and for the body's response to infections. Since chemokines and their derivatives are central in the pathophysiology of inflammatory and infectious diseases, those agents that exhibit a modulating, preferably antagonistic, activity of the chemokines and their receptors are useful in the therapeutic treatment of such inflammatory diseases. and infectious. The chemokine receptor CCR5 is of particular importance in the context of the treatment of inflammatory and infectious diseases. CCR5 is a receptor for chemokines, especially for the inflammatory proteins of macrophages (MIP) called MlP-la and MIP-1b, and for a protein which is regulated by activation and is expressed and secreted normally in T cells. RANTES). HIV-1 infects cells of the monocitomacrophagous line and 'helper T lymphocytes taking advantage of a high affinity interaction of the viral envelope glycoprotein (Env) with the antigen CD-4. Antigen CD-4, however, appears to be necessary, although not a sufficient requirement, to enter the cell and at least some other surface protein would be necessary to infect the cells (EA Berger et al., Ann. Rev. Immunol 1999 17: 657-700). It was subsequently discovered that either of the two chemokine receptors, CCR5 or CXCR4, were necessary for the infection of cells by the human immunodeficiency virus (HIV) as co-receptors in conjunction with CD4. The central role of CCR5 in the pathogenesis of HIV was inferred through the epidemiological identification of the potent modifying effects of the naturally occurring null allele CCR5? 32 disease. The mutation? 32 presents a deletion of 32 base pairs in the CCR5 gene giving rise to a truncated protein called? 32. Regarding the general population, homozygotes? 32 /? 32 are significantly frequent in exposed non-infected individuals suggesting the role of CCR5 in the entry of HIV into the cell (R. Liu et al., Cell 1996 86 (3) -. 361-311; M. Sa son et al. , Nature 1996 382 (6593): 722-725). The CD4-binding site in HIV gpl20 appears to interact with the CD4 molecule on the surface of the cell, and undergoes conformational changes that allow it to bind to another cell surface receptor, such as CCR5 and / or CXCR-4. This leads to the viral envelope to an approach to the cell surface and allows the interaction between gp41 of the viral envelope and a fusion domain on the cell surface, the fusion with the cell membrane, and the entry of the viral nucleus into the cell. Therefore, an agent that can block chemokine receptors in humans that present normal chemokine receptors will prevent infection in healthy individuals and slow down or stop viral progression in infected patients. It has been found that RANTES, a natural ligand for the CCR5 receptor, and a chemically modified analogue at the N-terminal end thereof, RANTES aminooxypentane, block the entry of HIV into the cells. (G. Simmons et al., Science 1997 276: 276-279). Other compounds have been shown to inhibit HIV replication, including soluble protein CD4 and synthetic derivatives thereof (Smith, et al., Science 1987 238: 1704-1707), dextran sulfate, Direct Yellow 50 dyes, Evans blue , and certain azo dyes (U.S. Patent No. 5,468,469). It has been shown that some of these antiviral agents act by blocking the binding between gpl20, the envelope protein of HIV, and its target, the cell's CD4 glycoprotein. In A-M. Vandamme et al. (Antiviral Chemistry & Chemotherapy, 1998 9: 187-203) current HAART clinical treatments for HIV-1 infections in humans including combinations of at least three drugs are revealed. Highly active antiretroviral therapy (HAART) has traditionally consisted in the combination of therapy with nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (Pl). These compounds inhibit biochemical processes required for viral replication. In patients who have never been subjected to this type of therapy before and who strictly follow the treatment, HAART is effective in reducing mortality and the progression of HIV-1 to AIDS. While HAART has dramatically altered the prognosis for people infected with HIV, there are many drawbacks to current therapy including highly complex dosing regimens and side effects that can be very serious (A. Carr and DA Cooper, Lancet 2000 356 (9239): 1423-1430). In addition, these multiple therapies do not eliminate HIV-1 and long-term treatment often results in multidrug resistance and therefore limits their usefulness in long-term therapies. The development of new therapies to provide better treatment of HIV-1 remains a priority. The investigation of different classes of modulators of chemokine receptor activity, especially that of the chemokine receptor CCR5, suggests the inhibition of CCR5 'as a new treatment modality. Suitable typical NRTIs include zidovudine (AZT) available as RETROVIR® from Glaxo-Wellcome Inc .; didanosine (ddl) available as VIDEX® from Bristol-Myers Squibb Co .; zalcitabine (ddC) available as HIVID® from Roche Pharmaceuticals; stavudine (d4T) available as ZERIT® from Bristol-Myers Squibb Co .; lamivudine (3TC) available "as EPIVIR® from Glaxo-ellcome; abacavir (1592U89) disclosed in WO96 / 30025 and available as ZIAGEN® from Glaxo-Wellcome; adefovir dipivoxil [bis (POM) -PMEA] available as PREVON® from Gilead Sciences; lobucavir (BMS-180194), a nucleoside reverse transcriptase inhibitor disclosed in EP-0358154 and EP-0736533 and under development of Bristol-Myers Squibb; BCH-10652, a reverse transcriptase inhibitor (in the form of a mixture) racemic of BCH-10618 and BCH10619) under development of Biochem Pharma; emitricitabine [(-) - FTC] authorized by Emory University under U.S. Patent No. 5,814,639 and under development of Triangle Pharmaceuticals; beta-l-FD4 (also known as beta -LD4C and called beta-1-2 ', 3' -dicleoxy-5-fluoro-cytidine) authorized by Yale University for Vion Pharmaceuticals; DAPD, the purine nucleoside, (-) -bD-2, 6-diamino- dioxolane purine disclosed in EP-0656778 and authorized by Emory University and the University o f Georgia for Triangle Pharmaceuticals; and lodenosine (FddA), 9- (2,3-dideoxy-2-fluoro-b-D-threo-pentofuranosyl) adenine, an inhibitor of purine-based reverse transcriptase and stable acid discovered by the NIH and under development by U.S. Bioscience Inc. Typical suitable NNRTIs include nevirapine (BI-RG-587) available as VIRAMUNE® from Roxane Laboratories; delaviradine (BHAP, U-90152) available as Pfizer RESCRIPTOR®; efavirenz (DMP-266) a benzoxazin-2-one disclosed in WO 94/03440 and available as SUSTIVA® from Bristol-Myers Squibb Co .; PNU-142721, a furopyridine-thiopyrimide under development by Pfizer 08807; AG-1549 (formerly Shionogi # S-1153); 5- (3,5-dichlorophenyl) thio-4-isopropyl-1- (4-pyridyl) methyl-1H-imidazol-2-ylmethyl carbonate disclosed in WO 96/10019 and under development by Agouron Pharmaceuticals, Inc .; MKC-442 (1- (ethoxy-methyl) -5- (1-methylethyl) -6- (phenylmethyl) - (2,4 (1H, 3H) -pyrimidinedione) discovered by Mitsubishi Chemical Co. and under development by Triangle Pharmaceuticals; and (+) -calanolide A (NSC-675451) and B, coumarin derivatives revealed at NIH U.S. Patent No. 5,489,697, authorized for Med Chem Research, which in turn is developing jointly with Vita-invest the (+) calanolide A as a product that can be administered orally.

Typical suitable PIs include saquinavir (Ro 31-8959) available in hard gel capsules as INVIRASE® and as soft gel capsules as FORTOVASE® from Roche Pharmaceuticals, Nutley, N.J. 07110-1199; ritonavir (ABT-538) available as NORVIR® from Abbott Laboratories; indinavir (MK-639) available as CRIXIVAN® from Merck & Co. , Inc .; nelfnavir (AG-1343) available with VIRACEPT® from Agouron Pharmaceuticals, Inc .; amprenavir (141W94), AGENERASE®, a non-peptidic protease inhibitor under development by Vertex Pharmaceuticals, Inc. and available from Glaxo-Wellcome, under an expanded-access program; Lasinavir (BMS-234475) available from Bristol-Myers Squibb; DMP-450, a cyclic urea discovered by Dupont and under development by Triangle Pharmaceuticals; BMS-2322623, an azapeptide under development by Bristol-Myers Squibb as a second-generation HIV-1 Pl; ABT-378 under development by Abbott; and AG-1549 an orally active imidazole carbamate discovered by Shionogi Shionogi and under development by Agouron Pharmaceuticals, Inc. Other antiviral agents include hydroxyurea, ribavirin, IL-2, IL-12, pentafuside. Hydroxyurea (Droxia), an inhibitor of ribonucleoside triphosphate reductase, the enzyme involved in the activation of T cells, was discovered in NCI and is under preclinical studies, it was shown to have a synergistic effect on the activity of didanosine and has been studied together with stavudine. IL-2 is revealed in Ajinomoto EP-0142268, Takeda EP-0176299, and Chiron Patentes Americans Nos. RE 33,653, 4,530,787, 4,569,790, 4,604,377, 4,748,234, 4,752,585, and 4,949,314, and is available as PROLEUKIN® (aldesleukin) in the form of a lyophilized powder for intravenous infusion or subcutaneous administration after reconstitution and dilution with water; a dose of 1 to about 20 million 1 U / day, the subcutaneous route is preferable; a dose of about 15 million 1 U / day, with the subcutaneous route being more preferable. IL-12 is disclosed in WO 96/25171 and is administered in a dose between about 0.5 μg / kg / day to about 10 μg / kg / day, the subcutaneous route is preferable. Pentafuside (FUZEON®), a synthetic peptide of 36 amino acids, disclosed in U.S. Patent No. 5,464,933 which acts by inhibiting the fusion of HIV-1 with the target membranes. Pentafuside (3-100 mg / day) is given to HIV-1 positive patients who are refractory to triple combination therapy in the form of continuous subcutaneous infusion or injection together with efavirenz and 2 PIs; the use of 100 mg / day is preferable. Ribavirin, l-.beta. -D-ribofuranosyl-lH-1,2,4-triazole-3-carboxamide is available from ICN Pharmaceuticals, Inc., Costa Mesa, Calif .; its manufacture and formulation are described in U.S. Patent No. 4,211,771.

In addition to the potential presented by modulators of CCR5 in the management of HIV infections, the CCR5 receptor is an important regulator of immune function and the compounds of the present invention can be valuable for the treatment of disorders of the immune system. It is also possible to treat rejection in the transplantation of solid organs, graft versus host disease, arthritis, rheumatoid arthritis, irritable bowel syndrome, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis, by means of administration, to those persons in need thereof, of an effective amount of a CCR5 antagonist compound of the present invention.

Pharmacokinetic studies in association with large molecules, proteins and peptides resulted in the establishment of programs for the identification of low molecular weight CCR5 antagonists. Efforts for the identification of chemokine modulators are reviewed in (W. Kazmierski et al., Biorg Med. Chem. 2003 11: 2663-76.; L. Agra al and G. Alkhatib, Expert Opin. Ther. Targets 2001 5 (3): 303-326; Chemokine CCR5 antagonists incorporating 4-aminopiperidine scaffold, Expert Opin. Ther. Patents 2003 13 (9): 1469-1473; M. A. Cascieri and M. S. Springer, Curr. Opin. Chem. Biol. 2000 4: 420-426, and references cited therein). The Takeda program was the first to obtain results with the identification of TAK-779 (M. Shiraishi et al., J. Med. Chem. 2000 43 (10): 2049-2063). Schering has advanced Sch-351125 in Phase I / II clinical studies and has contributed the advance of a compound with a higher tracking power, Sch-417690 in Phase I studies (SW McCrombie et al., WO 00066559, BM Baroudy et al. WO 00066558; A. Palani et al., J. Med Chem. 2001 44 (21): 3339-3342; JR Tagat et al., J. Med Chem. 2001 44 (21): 3343-3346; JA Esté, Cur Opin. Invest. Drugs 2002 3 (3): 379-383).

Seh-4í769v Scfrdnias Scfc «350 £ 3 Merck has disclosed the preparation of (2S) -2- (3-chlorophenyl) -1-N- (methyl) -N- (phenylsulfonyl) amino] -4- [spiro (2,3-dihydrobenzothiophene-3,4 '- piperidin-1 '-yl) butane S-oxide (1) and related derivatives, tri- substituted pyrrolidines and 3-piperidines substituted with a good affinity for the CCR5 receptor and potent HIV activity. (PE Finke et al., Bioorg, Med Chem. Lett., 2001 11: 265-270, PE Finke et al., Bioorg, Med Chem. Lett., 2001 11: 2469-2475, PE Finke et al. , Bioorg, Med. Chem. Lett., 2001 11: 2475-2479, JJ Hale et al., Bioorg, Med Chem. Lett., 2001 11: 2741-22745, D. Kim et al., Bioorg, Med. Chem. Lett., 2001 11: 3099-3102) 3 UK-4278S? WO 0039125 (DR Armor et al., And WO 0190106 (M. Perros et al A reveal heterocyclic compounds that are potent and selective CCR5 antagonists.) UK-427857 has advanced in clinical trials and shows activity against HIV-1 isolates and laboratory strains. (MJ Macartney et al., 43rd Intersci Conf. Antimicrob Agents Chemother. (September 14-17, 2003, Summary H-875 ' EP1236726 (H. Habashita et al.) Discloses the triazaspiro [5, 5] undecan derivatives exemplified by AK602 which modulates the cytokine receptors. The compounds are outside the scope of the present invention. (H. Nakata et al., Poster 546a, llth Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, February 8-11, 2004. Other analogues have also been disclosed, see, for example, K. Maeda et al., J Biol. Chem. 2001 276 (37): 3519435200) WO 03/057698 (N. Schlienger) describes compounds of l-oxa-3,8-diaza-spiro [4.5] decan-2-one. More specifically identified are compounds 4 of 3,4-di (optionally substituted) benzyl-l-oxa-3,8-diaza-spiro- [4.5] decan-2-one where R is an alkyl optionally substituted by a cycloalkyl, heterocyclic, heteroaryl or aryl ring. The compounds of the invention selectively modulate monoamine receptors for the 5HT2A receptor. The reference also shows, but does not exemplify, bicyclic compounds wherein R2 and R3 together form an alkyl chain. These l-oxa-3,8-diaza-spiro [4.5] decan-2-ones compounds and methods do not fall within the scope of the present invention. L-oxa-3, 8-diazaspiro [4.5] decan-2-ones 5, and 1, 3, 8-triazaspiro [4.5] decan-2-ones have been revealed as antagonists of the tachykinin NKa receptor (PW) Smith et al., J. Med. Chem. 1995 38 (19): 3772-79). It has been revealed that other compounds of l-oxa-3,8-diaza-spiro [4.5] decan-2-ones are capable of blocking a-adrenergic activity (JM Caroon et al., J. Med Chem. 1981 24 (11): 1320; RM Clark et al., J. Med. Chem. 1983 26 (6): 855-861). U.S. Pat. No. 3,399,192 (G. Regnier et al.) Discloses that the compounds of l-oxa-3, 8-diaza-spiro [4,5] decan-2-ones have activity as analgesics, central nervous system depressants and bronchodilators . EP414422 (E. Toth et al.) Discloses the usefulness of l-oxa-3,8-diaza-spiro [4.5] decan-2-one compounds as antiallergics and psychotropic agents.

JP 63208590 (Yamanouchi Pharmaceuticals KK) discloses the usefulness of compounds 6 of l-oxa-3,8-diaza-spiro [4,5] decan-2,4-dione in the treatment of disorders of the central nervous system. WO 2002102313 (J. Guo) discloses the utility of pyrimidine compounds containing the radical l-oxa-3,8-diaza-spiro [-4.5] decane-2,4-dione in the inhibition of phosphodiesterase. These compounds are outside the scope of the present invention. 1, 3, 8-Triaza-spiro [4.5] decan-4-one blocks the binding at the B2 receptor of bradykinin and antagonizes the actions mediated in vivo by bradykinin (B. J. Mavunkel et al.

J. Med. Chem. 1996 39 (16): 3169-73). Other related l-oxa-3, 8-diaza-spiro [4.5] decan-2-ones have been revealed: GB 1478932 (G. Regnier et al.) As antianaphylactic and bronchodilator compounds; J. Maillard, Eur. J. Med. Chem. 1974 9 (2): 128-132 as adrenolytic compounds; J. Maillard, Chim. Ther. 1972 7 (6): 458-466; J. Maillard, J. Med Chem. 1972 (11): 1123-1128 as analgesic and adrenolitic compounds; US 3,721,675 (J. Maillard). It has also been found that 1-oxa-3, 9-diazaspiro [5.5] undecan-2-ones have neuroleptic activity (J. Maillard, Eur. J. Med. Chem. 1974 9 (4): 416-42). WO 200130780 (RM Scarborough et al.) And WO 9711940 (JM Fisher) disclose the compounds that generically surround the ring of l-oxa-3,8-diazaspiro [4.5] decan-2-one as inhibitors of thrombosis and the platelet aggravation. WO 9965494 (M. W. Embry et al.) Discloses oxadiaza and triazaspiro [4.5] decylmethylimidazoles as well as their analogues as precursors of the prenyl protein transferase. 8 WO 200292604 (H. Cai et al.) Discloses compounds related to 9-benzoyl-5-phenyI-l-oxa-3,9-diaza-spiro [5.5] ndecan-2-ones 8, which are useful for treatment of diseases associated with the neurokinin receptor. WO 9711940 (M. J. Fisher et al.) Discloses 1-oxa-3,9-diaza-spiro [5, 5] undecan-2-one compounds as inhibitors of platelet aggregation mediated by fibrinogen. WO 200157044 (H. Horino et al.) Discloses the fused 1-oxa-3, 9-diazaiespiro [5.5] ndecan-2-ones which are antagonists of the monocyte-1 chemotactic protein (MCP-1). The compounds of 4-Substituted-l-oxa-3, 9-diazaspiro [5.5] undecan-2-ones have been revealed as possible possessors of neuroleptic properties (J. Bassus et al., Eur. J. Med. Chem. 1974 9 (4): 416-423). These compounds are outside the scope of the present invention. The present invention relates to compounds according to formula I, to the methods. for the treatment of diseases that can be alleviated by the administration of a compound according to the formula which is a CCR5 antagonist and to pharmaceutical compositions applicable in the treatment of diseases containing a compound according to formula I mixed with at least a vehicle, diluent or excipient. An object of the present invention is (i) a compound according to formula I, where: R12 is A is (CH2) q; R1 is C (= 0) R4, S (0) pR, or C (= 0) X, wherein X is NR5R6 or OR11; R2a and R2b are (a) independently hydrogen, C? _? 0 alkyl, C2_? Or alkenyl, Ca_10 haloalkyl, C3_7 cycloalkyl, C3_7 cycloalkyl-C? _3 alkyl, C? _? Heteroalkyl, C? _? 0 alkylidene , Ci-io-heteroalkylidene, aryl, aryl-C? _3 alkyl, heteroaryl, heteroaryl-C? -3 alkyl, C? _? 0 alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -0-, - S-, -NH- or -NR5-, - (CH2) WR8 where w is an integer between 2 and 6 ~, and the alkyl chain C2_6 optionally contains a double bond, - (CH2) WCH = NR9 where w is an integer between 2 and 6; or (b). , together with the carbon atoms to which they are attached, are o-phenylene optionally substituted with 1 to 3 substituents independently selected from the group consisting of C? _6 alkyl, C? -? haloalkyl, C? _6 alkoxy, C? _6 thioalkyl, C? _6 alkylsulfonyl, halogen, NR5aR6a, cyano and nitro with the proviso that if R2a, R2b, together with the carbon atoms to which they are attached are optionally substituted or phenylene, m is 1; R3 is C? -? Or alkyl, C2-? 0 alkenyl, C? _ Or heteroalkyl, C3_7 cycloalkyl, C? _6 alkyl-C3-cycloalkyl, C? _6 alkyl heterocyclic, aryl, aryl-C? _3 alkyl, heteroaryl , C? _6 alkyl heteroaryl, C (= 0) R3a wherein R3a is C? -? Or alkyl, C2_? Or alkenyl or C3_7 cycloalkyl, or a fragment of formula Ila-IIc; Ha nb He R 4 is Ci -ioalkyl, C3_7 cycloalkyl-Ci-io substituted alkyl, heterocycle, aryl, or heteroaryl; R5 and R6 are (a) H, C? _? 0 alkyl, C? -10 heteroalkyl, C3_7 cycloalkyl, C? _6 C3_7 alkyl cycloalkyl, C? _6 heterocyclic alkyl, aryl, aryl-C? Alkyl, heteroaryl, or alkyl heteroaryl when considered independently; or (b) C3_6 alkylene or [(CH2) 2] 20 when considered together; R5a and R6a are (a) hydrogen, C? _6 alkyl or C? _6 alkylcarbonyl when considered independently or (b) C3_6 alkylene or [(CH2) 2] 20 when considered together; R7 is hydrogen, cyano or C6-6 alkyl; R8 is -CN, -N02, -CONR5aR6a, COR9, ~ NHS02C? _6 alkyl; R9 is OH or C? -6 alkoxy; R10 is N or N + -OA R11 is C? _? Or alkyl, C? _? Heteroalkyl, C3_ cycloalkyl, C? _6 cycloalkyl, heterocycle-Ci-? Alkyl, aryl, aryl-C? Alkyl, heteroaryl, C ? 6 alkyl heteroaryl; m is 0 or 1; n is independently from 0 to 2; or is independently 0 or 1; p is from 0 to 2; q is from 1 to 3; wherein each of the aforementioned heteroaryls is independently selected from the group consisting of pyridyl, 1-oxy-pyridinyl, pyrimidyl, oxypyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, indolinyl , N-Boc-indolinyl, quinolinyl, isoquinolinyl, benzofuranyl, 4,5,6,7-tetrahydrobenzofuranyl and 1, 2, 3, 4-tetrahydroacridinyl; each of the above-mentioned aryls and heteroaryls are optionally independently substituted by 1 to 3 substituents selected from the group consisting of hydroxyl, C? _6 alkyl, C? _6 haloalkyl, C? _6 alkoxy, C? _6 haloalkoxy, C? _6 thioalkyl , aryl, aryl C? -3 alkyl, aryloxy, heteroaryloxy, thioaryl, thioheteroaryl, aryl C? 3 alkoxy, heteroaryl, heterocyclyl, C? -6 alkyl heterocycle, CX-6 alkylsulfonyl, -NHS02C? _6 alkyl, S02NR5aR6a, (CH2) UC02R9, (CH2) uCONR5aR6a, -XxC (= 0) X2, C? _? 0 alkylcarbonyl, halogen, NR5aR6a, cyano, nitro and C? _? Or alkyl wherein 2 or '3 non-adjacent carbon atoms are independently substituted with -O-, -S-, -NH- or NR5, wherein u is an integer from 0 to 6, X1 is NR5b or 0; X2 is NR5R6 or OR3 and R5b is H or C? -6 alkyl; each of the mentioned heterocycles is independently selected from the group consisting of pyrrolidinyl, 1-methyl-pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, tetrahydrofuranyl, dioxolanyl and pyranyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxy C? -6 alkyl, C? -6 haloalkyl, C? -6 alkoxy, C? _6 thioalkyl, C? _6 alkylsulfonyl, halogen, NR5aR6a 'cyano and nitro; pure enantiomers, partially resolved enantiomers, racemic mixtures, pharmaceutically acceptable acid addition salts, hydrates and solvates thereof. Other objects of the present invention are: (ii) the compound according to (i) having the formula Ia or Ib, the H > wherein: R2a and R2b are (A), independently hydrogen, C? _? 0 alkyl, C? -? or haloalkyl, C3_ cycloalkyl, C3_7 cycloalkyl-C? -3 alkyl, C? _10 heteroalkyl, C? _10 alkylidene, C? _10 heteroalkylidene, - (CH2) qR8, aryl, aryl-C? -3 alkyl, heteroaryl, heteroaryl-C? _3 alkyl, C? -? Or alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -0-, -S-, -NH- or -NR5-, or (B), together with the carbon atoms to which they are attached, are o-phenylene optionally substituted with 1 to 3 substituents independently selected from the group constituted by C? _6 alkyl, C? -6 haloalkyl, alkoxy, C? -6 thioalkyl,? -e alkylsulfonyl, halogen, NR5aR6a, cyano and nitro with the proviso that if R2a, R2b, together with the carbon atoms at the which are joined, optionally being o-phenylene substituted, m is 1; R3 is C? -? Or alkyl, C? -? Or heteroalkyl, C3_ cycloalkyl, C? _6 cycloalkyl, heterocycle C? _6 alkyl, aryl, aryl-C? _3 alkyl, heteroaryl, C? _6 alkyl heteroaryl; A, X, R1, R5, R6, R5a, R6a, R7, R8, R9, R10, R11, m, n, o, p, q, are as defined in (i). wherein each of the aforementioned heteroaryls are independently selected from the group consisting of pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl and isothiazolyl, each of the above mentioned aryls and heteroaryls are optionally substituted independently with 1 to 3 substituents selected from the group consisting of hydroxyl, C? _ alkyl, C? _6 haloalkyl, C? -6 alkoxy,? -β thioalkyl, C? _6 alkylsulfonyl, halogen, NR5aR6a cyano and nitro; each of said heterocycle are independently selected from the group consisting of pyrrolidinyl, 1-methyl-pyrrolidinyl; piperidinyl, tetrahydrofuranyl, and pyranyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl, C? _6 alkyl, C? _6 halpalkyl, C? -6 alkoxy, C? -6 thioalkyl, C? -iskylsulfonyl, halogen , NR5aR6, cyano and nitro, (iii). The compound according to (i) with formula le, R1 is C (= 0) R4, S (0) pR4, or C (= 0) X, wherein X is NR5R6 or OR11; R2a is C? -? Or alkyl, C? _? Or haloalkyl, C3_7 cycloalkyl, C3_7 cycloalkyl-C? _3 alkyl, C? _ Or heteroalkyl, C? -? Or alkylidene, C? -? Or heteroalkylidene or C? _? or alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -OR-, -S-, -NH- or -NR5-; R2b is hydrogen; R3 is C? -? Or alkyl, C3_7 cycloalkyl, C? -5 cycloalkyl, optionally substituted aryl, optionally substituted aryl-C? _3 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-C? _3 alkyl; R4 'is Ci -ioalkyl, optionally substituted aryl, optionally substituted heteroaryl; R7 is hydrogen, or C? _6 alkyl; m is 0 or 1; p is 2; X, R5, R6 and R11 are as defined in (i). (iv) The compound according to (iii) wherein R7 is hydrogen or methyl. (v) The compound according to (iii) wherein R1 is COR4; R2a is C? -? Or alkyl, C? -10 heteroalkyl or C? _10 alkyl wherein 2 or 3 carbon atoms not adjacent to the alkyl chain can be optionally substituted independently with -O-, -S-, - NH- or -NR5-; R 4 is optionally substituted aryl or optionally substituted heteroaryl. (vi) The compound according to (v) wherein R 4 is optionally substituted aryl. (vii) The compound according to (vi) wherein R 4 is optionally substituted phenyl. (viii) The compound according to (v) wherein R 4 is optionally substituted heteroaryl. (ix) The compound according to (viii) wherein R 4 is optionally substituted pyridyl, optionally substituted pyrimidyl, optionally substituted pyrazolyl, optionally substituted oxazolyl, optionally substituted isoxazolyl or optionally substituted pyrrolyl. (x) The compound according to (i) with the formula Id where A is (CH2) q; R2 is Cj-x or alkyl, C? _ Or haloalkyl, C3_7 cycloalkyl, C3_7 cycloalkyl-C? _3 alkyl, C? _? Heteroalkyl, C? _? 0 alkylidene, C? -? Or heteroalkylidene or C? _? 0 alkyl wherein 2 6 3 non-adjacent carbon atoms are independently substituted with -O-, -S-, -NH- or NR5; R3 is C? -? Or alkyl, C3_7 cycloalkyl, C? _6 cycloalkyl, optionally substituted aryl, optionally substituted aryl-Ca_3 alkyl, optionally substituted heteroaryl, optionally substituted-C? -3-heteroaryl alkyl; R 4 is optionally substituted aryl or optionally substituted heteroaryl; R7 is hydrogen or C? -6 alkyl; q is from 1 to 3. (xi) The compound according to (x) wherein A is (CH2) 2. (xii) The compound according to (i) with the formula le where R2a and R2b together with the carbon atoms to which they are attached are ortho-phenylene, optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl, C? -β alkyl, C? -6 haloalkyl, C? 6-alkoxy, C6-thioalkyl, C6-alkylsulfonyl, halogen, NR5aR6a, cyano and nitro; R3 is C? -? Or alkyl, C3_7 cycloalkyl, C? _6 alkyl-C3_7 cycloalkyl, optionally substituted aryl, optionally substituted aryl-C? _3 alkyl, optionally substituted heteroaryl, and optionally substituted heteroaryl-C? _3 alkyl; R 4 is optionally substituted aryl or optionally substituted heteroaryl; R5a and R6a are (A) hydrogen, C? -6 alkyl or? -β alkylcarbonyl when they are considered independently or (B) C3_6 alkylene or [(CH2) 2] 20 when considered together; R7 is hydrogen or C6-6 alkyl. (xiii) The compound according to any of (i) to (xii) to be used as a medicament. (xiv) The use of one or more compounds according to any of (i) to (xii) for the preparation of a medicament for the treatment or prevention of disorders, including those in which modulation of the CCR5 receptor is involved. ~ 5._. (xv) The use according to (xiv), wherein the disorder comprises diseases of the immune system as well as inflammatory diseases. (xvi) The use according to (xv), wherein the diseases comprising the infection of the human immunodeficiency virus (HIV), or the treatment of AIDS or ARC. (xvii) A pharmaceutical composition comprising an amount of a compound of (i) to (xii) therapeutically effective and at least one pharmaceutically acceptable carrier, diluent or excipient. The compounds and compositions of the present invention are useful for the treatment of diseases mediated by the human immunodeficiency virus in humans. Compounds and compositions of the present invention can also be used for the treatment of respiratory disorders, including acute respiratory distress syndrome (ARDS), bronchitis, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, asthma, emphysema, rhinitis and chronic sinusitis. Conditions that are triggered, affected or in some way correlated with T cells that are circulating in different organs can be treated by compounds of the invention. Compounds of the present invention may be useful for the treatment of these conditions and in particular, and without being limited thereto, for those in which a correlation with CCR5 or with CCR5 chemokines has been established: irritable bowel syndrome, including gastrointestinal Crohn's and ulcerative colitis, multiple sclerosis, rheumatoid arthritis, graft rejection, particularly though not limited to kidney and lung grafts, endometriosis, type I diabetes, kidney disease, chronic pancreatitis, inflammatory conditions of the lung or chronic heart failure For recent reviews of possible applications of chemokines and chemokine receptor blockers see: Cascieri, MA, and Springer, MS, The chemokine / 'chemokine receptor family: potential and progress for therapeutic intervention, Curr Opin. Chem. Biol. 2000 4 (4): 420-7; AEI Proudfoot The Strategy of Blocking the Chemokine System to Combat Disease, Immunol. 2000 177: 246-256. The term "an" entity as used herein refers to one or more of these entities; for example, a compound refers to one or more compounds or at least one compound. In this manner, the terms "one", "one or more", and "at least one" may be used interchangeably herein. The phrase "as defined above" refers to the first definition provided in the Summary of the Invention. The term "optional" or "optionally" as used herein means that the circumstance or event it describes may occur, but not necessarily, and that the description includes examples where the circumstance or event occurs and examples in which do not. For example, "optionally substituted" means that that part of the molecule can be hydrogen or a substitute. It is contemplated that the definitions described herein may be linked to give rise to 'chemically relevant combinations, such as "heteroalkylaryl", "haloalkylheteroaryl", "arylalkylheterocyclyl", "alkylcarbonyl", "alkoxyalkyl" and the like. The term "alkyl" as used herein denotes a branched or unbranched, saturated, monovalent residual hydrocarbon chain containing from 1 to 10 carbon atoms. The term "lower alkyl" denotes a linear or branched hydrocarbon chain residue containing from 1 to 6 carbon atoms. "C? _? O alkyl" as used herein refers to an alkyl composed of 1 to 10 carbons. Examples of alkyl groups include, but are not limited to, lower alkyl groups including methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl. When the term "alkyl" is used as a suffix following another term, as in "phenylalkyl," or "hydroxyalkyl," it refers to an alkyl group, as defined above, which is replaced by one or two substituents (preferably a substitute) selected from the other group specifically named. Thus, for example, "phenylalkyl" refers to an alkyl group having one or two phenyl substituents, and thus includes benzyl, phenylethyl, and biphenyl. An "alkylaminoalkyl" is an alkyl group having one or two alkylamino substituents. "Hydroxyalkyl" includes 2-hydroxyethyl, 2-hydroxypropyl, 1- (hydroxymethyl) -2-methylpropyl, 2-hydroxybutyl, 2,3-dihydroxybutyl, 2- (hydroxymethyl) -3-hydroxypropyl, and so on. Therefore, the term "hydroxyalkyl" as used herein defines a subset of subsequently defined heteroalkyl groups.The term "haloalkyl" as used herein means an alkyl group, as defined above, branched or unbranched, wherein 1, 2, 3 or more hydrogen atoms are substituted by a halogen. Examples thereof are 1-fluoromethyl, 1-chloromethyl, 1-bromomethyl, 1-iodomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 1-iodoethyl, 2-fluoroethyl, 2- chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-dichloroethyl, 3-bromopropyl or 2,2,2-trifluoroethyl. The term "cycloalkyl" as used herein denotes a saturated carbocyclic ring containing from 3 to 8 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. "C3_7 cycloalkyl" as used herein refers to a cycloalkyl composed of 3 to 7 carbons in the carbocyclic ring. The term "cycloalkyl alkyl" as used herein refers to the radical R'R "~, wherein R 'is a cycloalkyl radical as defined herein, and R" is an alkylene radical as defined herein, meaning that the point of attachment of the cycloalkylalkyl will be found in the alkylene radical. Examples of cycloalkylalkyl radicals include, but are not limited to, cyclopropylmethyl, cyclohexylmethyl, cyclopentylethyl. C3_7 cycloalkyl-C? _3 alkyl refers to the radical R'R "where R 'is C3-7 cycloalkyl and R" is C? _3 alkylene as defined herein. The term "heteroalkyl" as used herein means an alkyl radical, as defined herein, wherein one, two or three hydrogen atoms have been substituted by a substitute independently selected from the group consisting of -ORa, -NRbRc, and - S (0) nRd (where n is an integer of (0 to 2), it being understood that the point of attachment of the heteroalkyl radical is given through a carbon atom, where Ra is hydrogen, acyl, alkyl, cycloalkyl, or cycloalkylalkyl, Rb and Rc are independently hydrogen, acyl, alkyl, cycloalkyl, or cycloalkylalkyl, and when n is O, Rd is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl, and when n is 1 or 2, Rd is alkyl, cycloalkyl, cycloalkylalkyl, amino, acylamino, or alkylamino Alternatively, a heteroalkyl group is an alkyl radical wherein one or more carbon atoms is substituted by -0-, NRb-, or -S (0) n- Representative examples include, although they are not limited to them, 2-hydrox Ithyl, 3-hydroxypropyl, 2-hydroxy-1-hydroxymethylethyl, 2,3-dihydroxypropyl, 1-hydroxymethylethyl, 3-hydroxybutyl, 2,3-dihydroxybutyl, 2-hydroxy-1-methyl-propyl, 2-aminoethyl, 3- aminopropyl, 2-methylsulfonylethyl, aminosulfonylmethyl, aminosulfonylethyl, aminosulfonylpropyl, methylaminosulfonylmethyl, methylaminosulfonylethyl, methylaminosulfonylpropyl and the like. The term "alkylene" as used herein denotes a linear saturated divalent hydrocarbon radical of 1 to 10 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 10 carbon atoms, unless otherwise indicated. Examples of alkylene radicals include, but are not limited to, methylene, ethylene, propylene, 2-methyl-propylene, butylene, and 2-ethylbutylene. The term "heteroalkylidene" or "heteroalkylidene" as used herein means a bivalent radical = CRR ', wherein R is a heteroalkyl radical, a haloalkyl radical, an alkyl radical, or hydrogen, and R' is a heteroalkyl radical or a radical haloalkyl, as defined herein. Examples of heteroalkylidenyl radicals include, but are not limited to, 3, 3, 3-trifluoro-propylidenyl, 2-hydroxybutylidenyl, 3-amino-propylidenyl, and the like. The term "aryl" as used herein indicates a monovalent aromatic carbocyclic radical containing from 5 to 15 carbon atoms that form an individual ring, or one or more fused rings in which at least one ring is aromatic in nature, which may be optionally substituted with one or more, preferably one or three substituents independently selected from hydroxyl, thio, cyano, alkyl, alkoxy, lower haloalkoxy, alkylthio, halogen, haloalkyl, hydroxyalkyl, nitro, alkoxycarbonyl, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl, alkylsulfonyl, arylsulfinyl , alkylaminosulfonyl, arylaminosulfonyl, alkylsulfonylamino, arylsulfonylamino, carbamoyl, alkylcarbamoyl and dialkylcarbamoyl, arylcarbamoyl, alkylcarbonylamino, arylcarbonylamino, unless otherwise indicated. Alternatively two adjacent atoms of the aryl ring can be substituted with a methylenedioxyl or ethylenedioxyl group. Examples of aryl radicals include, but are not limited to, phenyl, naphthyl, indanyl, anthraquinolyl tetrahydronaphthyl, 3,4-methylenedioxyphenyl,. 1, 2, 3, 4-tetrahydroquinolin-7-yl, 1, 2, 3, 4-tetrahydroisoquinolino-7-yl and the like. The term "arylalkyl" or "aralkyl" as used herein denotes the radical R'R "-, wherein R 'is an aryl radical as defined herein, and R" is an alkylene radical as defined herein with the understanding that the point of attachment of the arylalkyl will be found in the alkylene radical. Examples of arylalkyl radicals include, but are not limited to, benzyl, phenylethyl and 3-phenylpropyl. The term "heteroaryl" or "heteroaromatic" as used herein means a monocyclic or bicyclic radical of 5 to 12 ring atoms, having at least one aromatic ring, containing four to eight atoms per ring, incorporating one or more heteroatoms N, O, or S, the remaining atoms of the ring being carbon, understanding that the point of attachment of the heteroaryl radical will be found in an aromatic ring. As is well known to those skilled in the art, heteroaryl rings have a less aromatic character than their fully carbon-based counterparts. Thus, for the purposes of the invention, a heteroaryl group needs to have only some degree of aromatic character. Examples of heteroaryl include monocyclic aromatic heterocycles having 5 to 6 ring atoms and 1 to 3 heteroatoms and include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, oxazole, isoxazole, thiazole , isothiazole, triazolino, thiadiazole and oxadiaxolino which may be optionally substituted by one or more, preferably - one or two substituents selected from hydroxyl, cyano, alkyl, alkoxy, thio, lower haloalkoxy, alkylthio, halo, haloalkyl, alkylsulfinyl, alkylsulfonyl, halogen, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl, nitro, alkoxycarbonyl and carbamoyl, alkylcarbamoyl, dialkylcarba oyl, arylcarbamoyl, alkylcarbonylamino and arylcarbonylamino. Examples of bicyclics include, but are not limited to, quinolinyl, isoquinolinyl, benzofuryl, benzothiophenyl, benzoxazole, benzisoxazole, benzothiazole and benzisothiazole. The bicyclics may be optionally substituted in any ring. The term "heteroarylalkyl" or "heteroaralkyl" denotes the radical of the formula R'R ", wherein R 'is an optionally substituted heteroaryl radical as defined herein, and R" is an alkylene radical as defined herein with the understanding that the point of attachment of the heteroaryl radical will be found in the alkylene radical. Examples of heteroarylalkyl radicals include, but are not limited to, 2-imidazolylmethyl, 3-pyrrolylethyl. The term "heterocyclyl" or "heterocycle" as used herein denotes a monovalent saturated cyclic radical, consisting of one or more rings, preferably one to two rings, of three to eight atoms per ring, incorporating one or more ring heteroatoms ( chosen from N, 0 or S (O) 0-2) r and which may optionally and independently be substituted by one or more, preferably one or two substituents selected from hydroxyl, oxo, cyano, lower alkyl, lower alkoxy, lower haloalkoxy, alkylthio, halo, haloalkyl, hydroxyalkyl, nitro, alkoxycarbonyl, amino, alkylamino, alkylsulfonyl, aryisulfonyl, alkylaminosulfonyl, arylaminosulfonyl, alkylsulfonylamino, arylsulfonylamino, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, unless otherwise indicated. Examples of heterocyclic radicals include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, oxazolidinyl, isoxazolidinyl, morpholinyl, piperazinyl, piperidinyl, tetrahydropyranyl, thiomorpholinyl, quinuclidinyl. The term "alkoxy group" as used herein denotes an -O-alkyl group, wherein alkyl is, as defined above, methoxy, ethoxy, n-propyloxy, i-propyloxy, u-butyloxy, 1- butyloxy, t-butyloxy, pentyloxy, hexyloxy, including its isomers. "Lower alkoxy" as used herein denotes an alkoxy group with a "lower alkyl" group as previously defined. "Ci-io alkoxyl" as used herein refers to "- an -0- alkyl wherein the alkyl is C? _ 0. The term" alkylthio "or" thioalkyl "denotes., A group -S- alkyl, wherein alkyl is, as defined above, methylthio, ethylthio, n-propylthio, n-butylthio, hexylthio, including its isomers. "Lower alkylthio" or "lower thioalkyl" as used herein denotes an alkylthio group with a group "lower alkyl" as previously defined "C? -? or alkylthio" as used herein refers to an -S-alkyl wherein the alkyl is C? -? 0 The terms "alkylsulfonyl" and "aryisulfonyl" as used herein they indicate a group of formula -S (= 0) 2R wherein R is respectively alkyl or aryl, and alkyl and aryl are as defined herein The term "halogen" or "halo" as used herein indicates fluorine, chlorine, bromine, or iodine The term "phenylene" as used herein refers to the radical C6H4 = benzene derivative by substitution of 2 H atoms. omeros, orto (o-), meta (m-) and para (p-). The term "acyl" as used herein denotes a group of formula -C (= 0) R wherein R is hydrogen or lower alkyl as defined herein. The term "alkylcarbonyl" as used herein denotes a group of formula C (= 0R wherein R is alkyl as defined herein The term "arylcarbonyl" as used herein denotes a group of formula C (= 0R wherein R e an aril group; the term "beñzoilo" as used herein means an "arylcarbonyl" group in which R is phenyl. The compounds of formula I exhibit tautomerism. Tautomeric compounds can exist as two or more interconvertible species. Prototropic tautomers result from the migration of a hydrogen atom covalently bound between two atoms. Tautomers generally exist in equilibrium and attempts to isolate an individual tautomer usually produce a mixture of physical and chemical properties of a mixture of compounds. The equilibrium position depends on the chemical characteristics of the molecule. For example, in many aliphatic ketones and aldehydes, such as acetaldehyde, the keto form predominates, while in phenols, the enol form predominates. The most frequent prototropic tautomers include the keto / enol tautomers (-C (= 0) -CH- < -C (-OH) = CH-), amide / imidic acid (-C (= 0) -NH- <? -C (-OH) = N-) and amidine '(-C (= NR) -NH- < - > -C (-NHR) = N-). The latter two are particularly frequent in the heteroaryl and heterocyclic rings and the present invention encompasses all tautomeric forms of the compounds. It will be appreciated by those skilled in the art that the compounds of the formula la and Ib may contain one or more chiral centers and, therefore, exist in two or more stereoisomeric forms. Racemates of these isomers, individual isomers and mixtures enriched in one enantiomer, as well as diastereomers when there are two chiral centers, and mixtures partially enriched with specific diastereomers are within the scope of the present invention. It will also be appreciated by those skilled in the art that replacement of the troop-ring can not occur in either the endo- or exo- configurations, and the present invention encompasses both configurations.

The present invention includes all individual stereoisomers (e.g. enantiomers), racemic mixtures or partially resolved mixtures of the compounds of the formula la and Ib and, where appropriate, the individual tautomeric forms thereof. The racemates can be used as such or can be resolved in their individual isomers. The resolution can provide stereochemically pure compounds or mixtures enriched in one or more isomers. The methods for the separation of isomers are well known (see Allinger N.

L. and Eliel E. L. in "Topics in Stereochemistry", Vol. 6, Wiley Interscience, 1971) and include physical methods such as chromatography using a chiral adsorbent. The individual isomers can be prepared in chiral form from chiral precursors. Alternatively, the individual isomers can be chemically separated from a mixture by the formation of diastereomeric salts with a chiral acid, such as the individual enantiomers of 10-camforsulfonic acid, camphoric acid, acid. alpha.- bromocamhoric, tartaric acid, diacetyltartaric acid, malic acid, pyrrolidone-5-carboxylic acid, and the like, crystallizing the salts fractionally, and then releasing one or both resolved bases, optionally repeating the process, to obtain independently a another or both substantially free of the other; that is, in a form that exhibits an optical purity > 95% Alternatively the racemates may be covalently linked to a chiral compound (auxiliary) to produce diastereomers which can be separated by chromatography or by fractional crystallization after which the chiral auxiliary is chemically removed to yield pure enantiomers. The compounds of formulas la or Ib contain at least two basic centers and form suitable acid addition salts from acids that form non-toxic salts. Examples of salts of inorganic acids include chloride, bromide, iodide, sulfate, bisulfate, nitrate, phosphate, hydrogen phosphate. Examples of salts of organic acids include acetate, fumarate, pamoate, aspartate, besylate, carbonate, bicarbonate, camsylate, D and L-lactate, D and. L-tartrate, esylate, mesylate, malonate, orotate, gluceptate, methylisulfate, stearate, glucuronate, 2-napsylate, tosylate, hybienate, nicotinate, islet, malate, maleate, citrate, gluconate, succinate, saccharate, benzoate, esylate, and salts of pamoato. For a review on appropriate salts see Berge et al, J. Pharm. Sci., 66, 1-19, 1977. The term "solvate" as used herein denotes a compound of the invention or a salt thereof, which it also includes a stoichiometric or non-stoichiometric amount of a solvent non-covalently linked by intermolecular forces.Preferable solvents are those which are volatile, non-toxic, and / or acceptable for administration to humans in trace amounts. used herein denotes a compound of the invention or a salt thereof, which also includes a stechymetric or non-stoichiometric amount of water non-covalently bound by intermolecular forces.The term "clathrate" as used herein indicates a compound of the invention or a salt thereof in lattice-crystal form containing spaces (eg, channels) that present a molecule (eg, a solvent or water) trapped therein. and used here refers to the strain of HIV virus that has the dominant genotype that occurs naturally in the normal population that has not been exposed to reverse transcriptase inhibitors. The term "wild-type reverse transcriptase" as used herein refers to the reverse transcriptase expressed by the wild-type strain that has been sequenced and deposited in the SwissProt database with accession number P03366. The term "reduced susceptibility" as used herein refers to a change in sensitivity of about 10 timesor higher, of a given viral isolate in comparison to the sensitivity shown by the wild virus in the same experimental system. The term "nucleoside and nucleotide reverse transcriptase inhibitors" ("NRTI" s) as used herein means nucleosides and nucleotides and analogs thereof that inhibit the activity of HIV-1 reverse transcriptase, the enzyme that catalyzes the conversion of HIV-1 genomic viral RNA in proviral DNA of HIV-1. The term "non-nucleoside reverse transcriptase inhibitors" ("NNRTI" s) as used herein denotes non-nucleosides that inhibit the activity of HIV-1 reverse transcriptase. The term "protease inhibitor" ("Pl") as used herein indicates inhibitors of the HIV-1 protease, an enzyme required for the proteolytic cleavage of the viral polyprotein precursors (eg, the GAG and the viral polyproteins). GAG Pol), in individual functional proteins found in infectious HIV-1. HIV protease inhibitors include compounds having a peptidomometic structure, high molecular weight (7600 daltons) and a substantial peptide character, for example, CRIXIVAN as well as non-peptide protease inhibitors for example, VIRACEPT. The following abbreviations are used throughout this specification and in the claims: (atm) atmospheres, (BBN or 9-BBN) 9-borabicyclo [3.3.1] nonane, (Boc) tert-butoxycarbonyl, ((BOC) ) di-tert-butyl pyrocarbonate or boc anhydride, (Bn) benzyl, (Bu) butyl, (cbz or Z) benzyloxycarbonyl, (DABCO) diazabicyclooctane, (DAST) diethylaminosulfide trifluoride, (DBU) 1,8-diazabicyclo- [ 5.4.0] undec-7-ene, (DCE) 1,2-dichloroethane, (DCM) dichloromethane, IDEAD) diethyl azodicarboxylate, (DIAD) di-iso-propylazodicarboxylate, (DEIPA) diethyl iso-propylamine, (DIBAL-H ) di-iso-butylaluminum hydride, (DMA) N, N-dimethyl acetamide, (DMAP) 4-N, N-dimethylaminopyridine, (DMF) N, N-dimethylformamide, (dppf) 1,1 '-bis- ( diphenylphosphino) -ferrocene, (EDCI) 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, (EtOAc) ethyl acetate, (Et20) diethyl ether, (Et) ethyl, (EtOH) ethanol, (LiHMDS) hexa ethyl disilazane of lithium, (HOAc) acetic acid, (HPLC) liquid chromatography of alt pressure, (i-Pr) iso-propyl, (Me) methyl, (MeCN) acetonitrile, (MeOH) methanol, (MTBE) methyl t-butyl ether, (mp) melting point, (ms) mass spectrum, (NBS) ") N-bromosuccinimide, (NMP) N-methylpyrrolidone, (PCC) pyridinium chlorochromate, (PDC) pyridinium dichromate, (Pr) propyl, (psi) pounds per square inch, (pir) pyridine, (ta or TA) room temperature, (TEA or Et3N) triethylamine, (THF) triflate CF3S02-, (TFA) trifluoroacetic acid, (THF) tetrahydrofuran, (TLC) thin layer chromatography, (TMHD) 2, 2, 6, 6-tetramethylheptane-2 , 6-dione, (TsOH) p-toluenesulfonic acid monohydrate. Examples of representative compounds within the scope of the present invention are provided in the following Table. These examples and following preparations are provided to enable those skilled in the art to further understand as well as to allow the practice of the present invention. They should not be considered as limiting the scope of the invention, but as merely illustrative and representative of it. In general, the nomenclature used in this invention present invention. They should not be considered as limiting the scope of the invention, but as merely illustrative and representative of it. In general, the nomenclature used in this application is based on AUTONOM ™ v.4.0, a computerized system of the Beilstein Institute for generating IUPAC systematic nomenclature. If there is any discrepancy between a structure represented and the name given to it, the structure represented should be considered of greater importance. In addition, if the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or marked lines, the structure or portion of the structure should be construed as encompassing all stereoisomers thereof. -153 2- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l- 549 oxa-3, 9-diaza-spiro [5.5] undec-9-yl) -piperidine-1-carbonyl] -3 -methylbenzonitrile -154 5-Butyl-3-enyl-3-cyclohexylmethyl-9- [1- 536 (2,6-dimethyl-benzoyl) -piperidin-4-yl] -1-oxa-3, 9-diaza -spiro [5.5] undecan-2-one -155 5-Butyl-3-cyclohexylmethyl-9- [4-methyl-1- 572 (2,4,5-trimethyl-thiophene-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5.5] undecan-2-one -156 5-Bu.ethyl-3-cyclohexylmethyl-9- [4-methyl-1- (5-1605 methyl-3-phenyl) -isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5.5] undecan-2-one; compound with trifluoroacetic acid -157 5-Butyl-9-. { l- [4,6-Dimethyl-2- (pyridin-2, 537-yloxy) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5.5] undecan-2-one; compound with trifluoroacetic acid -158 4-Butyl-3-cyclohexylmethyl-8- [1- (3,5- 565 dicholoro-pyridine-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza -spiro [4.5] decan-2-one -159 (S) -4-Butyl-3-cyclohexylmethyl-8- [1- (2,6- 524 dimethyl-benzoyl) -piperidin-4-yl] -1-oxa - 3, 8-diaza-spiro [4.5] decan-2-one -160 (R) -4-Butyl-3-cyclohexylmethyl-8 - [1- (2,6- 524 dimethyl-benzoyl) -piperidin-4 -yl] -1-oxa-3,8-diaza-spiro [4 .5] decan-2-one (S) -5-Butyl-3-Cyclohexylmethyl-9- [1- (2, 6- 538 1-191 dimethyl-benzoyl) -piperidin-4-yl] -1-oxa-3, 9-diaza-spiro [5.5] undecan-2-one 1-192 4-Butyl-3-methyl-8- [1- (2,4,6-trimethyl-456,8-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4.5] decan-2-one; compound with] 1-193 trifluoroacetic acid 4-Butyl-8- [1- (2,6-dichloro-benzoyl) -482.7 piperidin-4-yl] -3-methyl-l-oxa-3, 8-diaza-spiro [4.5] decan-2-one; compound coni trifluoroacetic acid 1-194 4-Butyl-8- [1- (2-chloro-6-methyl-benzoyl) - 462.7 piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza- spiro [4.5] decan-2-one; composed with | 1-195 trifluoroacetic acid 4-Butyl-8- [1- (2,6-dichloro-4-methyl-469.7-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza- spiro [4.5] decan-2-one; Compounded with 1-196 trifluoroacetic acid 4-Butyl-8- [1- (4-methoxy-2,6-dimethyl-472.8-benzoyl) -piperidin-4-yl] -3-methyl-1-oxa- 3, 8- diaza-spiro [4.5] decan-2-one; compound with 1-197 trifluoroacetic acid 8- [1- (4-Butoxy-2,6-dimethyl-benzoyl) -514.8 piperidin-4-yl] -4-butyl-3-methyl-l-oxa-3, 8- diaza-spiro [4.5] decan-2 -one; compound with trifluoroacetic acid The following examples and preparations are provided to enable those skilled in the art to better understand as well as to allow the practice of the present invention. They should not be considered as limiting the scope of the invention, but as merely illustrative and representative of it. Efforts have been made to ensure accuracy with respect to the numbers used (for example, quantities, temperatures), but the possibility of allowing certain experimental errors and deviations, including differences in calibration, rounding of figures, and the like, is also contemplated. The compounds of the present invention can be made by means of a variety of methods represented in the illustrative synthetic reaction schemes which are shown and described below. The starting materials and reagents used in the preparation of these compounds are generally available from commercial suppliers, such as Aldrich Chemical Co., or are prepared by methods known to those skilled in the art following methods described in the references set forth in continuation Fieser and Fieser's Reagents for Organic Synthesis; Wiley & Sons: New York, Volumes 1-21; R. C. LaRock, Comprehensive Organic Transformations, 2nd. Wiley-VCH edition, New York 1999; Comprehensive Organic Synthesis, B. Trost and I. Fleming (Eds.) Vol. 1-9 Pergamon, Oxford, 1991; Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees (Eds) Pergamon, Oxford 1984, vol. 1-9; Comprehensive Heterocyclic Chemistry II, A. R. Katritzky and C. W. Rees (Eds) Pergamon, Oxford 1996, vol. 1-11; and Organic Reactions, Wiley & Sons: New York, 1991, Volumes 1-40. The following synthetic reaction schemes are merely illustrative of some methods by means of which the compounds of the present invention can be synthesized, various modifications of these synthesis reaction reaction schemes can be made and will be recommended to those skilled in the art. who want to refer to the disclosure contained in this application. The starting materials and intermediates of the synthesis reaction schemes can be isolated and purified using conventional techniques, including but not limited to filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectrum data. Unless otherwise specified, the reactions described herein are preferably carried out in an inert atmosphere at atmospheric pressure and in a range of reaction temperatures of about -78 ° C to about 150 ° C, preferably around from 0 ° C to about 125 ° C, and more preferably and conveniently around room temperature, for example, around 20 ° C. Some compounds of the following reaction schemes are represented by generalized substituents; however, those skilled in the art will appreciate immediately that the nature of the R groups may vary to allow for the variety of compounds contemplated by this invention. In addition, the reaction conditions are exemplary with alternatives well known to them. The reaction sequences in the following examples should not be construed as limiting the scope of the invention as set forth in the claims. The ring system of l-oxa-3, 8-diaza-spiro [4.5] decan-2-one can be assembled from an N-protected derivative of 4-oxo-piperidine. The precursor 4-piperidone is commercially available or, alternatively, it can be prepared by cyclization of the ethyl ester of the acid 3- (2-ethoxycarbonyl-ethylamino) -propionate (L. Ruzicka et al., Helv. Chim, Acta 1920 3: 812). While in Reaction Scheme 1 the (Z = C02CH2Ph) benzyloxycarbonyl protecting group is represented, which is easily introduced by standard protocols using benzyloxycarbonyl chloride, it will be appreciated that a variety of other well-known nitrogen protecting groups can also be sufficient (TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, Wiley &Sons, New York 1999). The construction of the oxazolidinone ring follows the general lines of the route described by P. W. Smith et al. (J. Med. Chem. 1995 38: 3772) and J. M. Caroon et al. (J. Med. Chem. 1982 24: 1320). REACTION SCHEME 1 lß lt- u 13 U R * ** tiJGkßrf M The butyric acid dianion was treated with 4-oxopiperidine-l-carboxylic acid benzyl ester to provide the tertiary carbinol lia. The carboxylic acid dianions (JC Stowell, Carbanions in Organic Synthesis, Wiley-Interscience, New York, 1979, pp.127-216, N. Petragnani et al., Synthesis 1982 521) are prepared by treatment of the carboxylic acid with two equivalents of base. While the reaction proceeds conveniently with lithium diisopropylamide, a variety of other strong non-nucleophilic bases, for example 2,2,6,6'-tetramethylpiperidine lithium or lithium hexamethyldisilazane can also be used. The base and the carboxylic acid are usually combined at -78 ° C and the initially formed carboxylic salt is heated from 0 to 20 ° C to produce the dianion quantitatively. The reaction is carried out in inert polar solvents with THF, dioxane, dimethoxyethane being commonly used. By using different carboxylic acids the substitute in the 4-position of the oxazolidone can be easily modified. A variant of the Curtius reaction is used to introduce the nitrogen atom and, concomitantly, generate a reactive acyl species that traps the hydroxyl group and completes the formation of the spiro ring. The characteristic feature of the Curtius type rearrangement of acyl acids is the loss of nitrogen and the formation of a positively charged "nitronium ion" that undergoes a 1,2-alkyl change and produces an isocyanate that traps alcohol. Diphenoxyphosphoryl azide (DPPA) has been shown to be a convenient reagent for forming acyl acid in situ. Variations that can be used to convert a derivative of a carboxylic acid to the corresponding amine include the reactions of Hofmann, Schmidt or Lossen (J. March Advanced Organic Chemistry 4th Ed J Wiley &Sons: New York, 1991; pp 1090- 1095, T. Shioiri Degradation Reactions in Comprehensive Organic Synthesis, vol 6, E. Winterfeldt (Ed) Pergamon, Oxford 1991 pp 795-825). The alkylation of an amide is carried out by treating an amine or a metal salt of the amine (for example a deprotonated form) with a compound RZ1 wherein Z1 is a halo, C4-4 alkenesulfonyloxy, benzenesulfonyloxy or p-type group. toluenesulfonyloxy, optionally in the presence of a base and / or a phase transfer catalyst. The reaction is usually carried out in the presence of a base such as triethylamine or N, N-diisopropylethylamine; DBU (1,8-diazabicyclo [5, 4, 0] undec-7-ene; or from an inorganic base such as Na 2 CO 3, NaHCO 3, K 2 CO 3 or Cs 2 CO 3: optionally in the presence of a phase transfer catalyst, and in a solvent such as acetonitrile, DMF (dimethylformamide), DMSO (dimethylsulfoxide), 1,4-dioxane, THF or toluene A metal salt can be formed by the treatment of the amide with a base such as sodium or potassium hydride, lithium diisopropyl amide, potassium tert-butoxide or sodium amylate in an unprotonated solvent such as THF, DMF or 1,4-dioxane which is then treated with a RZA compound. The introduction of a substitute into the urethane nitrogen was achieved by N-alkylation of the sodium salt of the amine which was generated by the treatment of 12 with sodium hydride and subsequent treatment of the salt with an alkylhalide to give ludar to 13. The removal of the carbobenzyloxy protecting group is carried out by means of catalytic hydrogenation. of deprotection be n, indeed, varied according to the nature of the N-protector group. Acidic conditions can be used to remove a benzyloxycarbonyl protecting group. The tert-butoxycarbonyl is a convenient alteration of the benzyloxycarbonyl protecting group which is removed in the trifluoroacetic acid treatment. Those skilled in the art will recognize that alternative protective groups can be used interchangeably and can alter the conditions of deprotection. The incorporation of the second piperidine ring is carried out by reductive amination of an N-acyl 4-piperidone. The reductive amination is preferably developed by combining an amine and a carbonyl compound in the presence of a complex metal hydride such as sodium borohydride, lithium borohydride, sodium cyanoborohydride, zinc borohydride, sodium triacetoxyborohydride or borane / pyridine conveniently at pH between 1-7, optionally in the presence of a dehydrating agent such as molecular sieve or Ti (IV) (0-i-Pr) 4 to facilitate the formation of the imine intermediate and at room temperature or with hydrogen in the presence of a hydrogenation catalyst, example in the presence of palladium / carbon, at a hydrogen pressure of 1 to 5 bar, preferably at temperatures between 20 ° C and the temperature of. boiling of the solvent used. The protection during the reaction of the reactive groups can also be advantageous by conventional protecting groups which will be cleaved again by conventional methods after the reaction. For a review of reductive amination methods have been reviewed: R. M. Hutchings and M. K. Hutchings Reduction of C = N to CHNH by Metal Hydrides in Comprehensive Organic Synthesis col. 8, I. Fleming (Ed) Pergamon, Oxford 1991 pp. 4754.

REACTION SCHEME 2 2, 6-diMe-benzoic acid PyBOP To prepare compound libraries, the availability of an advanced intermediary that can be reacted with a variety of fragments is often advantageous. In this way an alternative reaction scheme (Reaction scheme 2) is presented for carrying out the reductive alkylation of 14 with 10 (R = CBZ or Boc) reductive amination and subsequent de-protection of the piperidine nitrogen giving rise to Acylation of the free amine by 2,6-dimethylbenzoic acid gives rise to 16; however, it can be readily appreciated that 17 can be acylated or alkylated with a variety of compounds to give a chemical library with various piperidine functionalities which can be used for the identification and optimization of programs. The amidation of 17 can occur by conventional amide bond formation techniques such as the initial activation of a carboxylic acid either as an acid chloride or an acid anhydride. The activated acid and amine 17 can be reacted in the presence of an excess of a suitable base, for example, Na 2 CO 3, NaHCO 3, K 2 CO 3, triethylamine or N, -diisopropylethylamine, and in a suitable solvent, for example, dichloromethane, ethyl acetate , THF or toluene, with or without water as an accompanying solvent, Alternatively an ester and an amine, or a metal salt thereof, can react together in the presence of a base, for example triethylamine, and an optional catalyst in a solvent such as - dichloromethane, ethyl acetate, THF or toluene In another alternative the acid can be activated with 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (WCDI), 1, 1-carboniidiimidazole (CDI) or 1 , 3-dicyclohexylcarbodiimide (DCC) and l-hydroxy-7-azabenzotriazole (HOAT) or 1-hydroxybenzotriazole hydrate (HOBT), and reacted with the amine in the presence of a base, for example triethylamine, in a solvent such as THF, dichloromethane or toluene, experts in the field appreciate The existence of many alternatives to the reagents identified above that are capable of activating a carboxylic acid in a similar manner will be recognized. These reactions are typically carried out at moderately reduced temperatures between -10 to +10 ° C and are typically completed in several hours. The product is recovered by conventional means.

The secondary amine 17 can also be converted to sulfonamides (17a; R = S02Z1 where Z1 is alkyl or aryl) by treating with aryl sulfonyl chlorides under Schotten-Bauman conditions. The ureas and thioureas (17a: R = C0NR'R "or CSNHR 'R") are also accessible from -17. The procedures for the preparation of ureas and thioureas have been described in (J. Barluenga et al. a Thiocarbonil Group Bearing Two Heteroatoms Other than Halogen or a Chalcogen, in Comprehensive Organic Functional Group Transformations, vol 6, Thomas L. Gilchrist (ed) Elsevier Science Ltd., Oxford UK). The alkyl or aryl isothiocyanates are reacted with ammonium, primary and secondary amines to give, respectively, 1-substituted, 1,3-disubstituted and trisubstituted thioureas. This reaction is generally productive when it occurs in polar solvents such as diethyl ether, ethanol, water and acetone which are normally preferred. Alternatively an amine can be treated with a phosgene or a phosgene equivalent (for example carbonyl diimidazole) and give an aminocarbonyl chloride which is treated with ammonium, primary or secondary amines. The thioureas are prepared by analogous procedures using isothiocyanates or thiophosgene an equivalent thereof. REACTION SCHEME 3 : M = Boe Í8? M ~ »? C MiMgßr t, 0 The introduction of a methyl radical in position 4 was achieved by the treatment of the amino nitrile intermediate 18 of the Ti (Oi-Pr) 4 catalyzed condensation of 14 and N-BOC-4-oxopiperidine with diethylaluminum cyanide and subsequently substituting the nitrile for magnesium methyl bromide to give rise to 19 (A. Palani et al., J. Med. Chem. 2001 44 (21): 3339-42).

REACTION SCHEME 4 Compounds of 4-alkylidenyl (23: R '= alkyl), 4-aralkylidenyl (23: R' = aralkyl), 4-heteroarylalkyl-idenyl Y23: R '= heteroarylalkyl) and 4-heterocycloalkyl-idenyl (23: R' = heterocyclylalkyl) can be prepared by exploiting the susceptibility of acetylenes to nucleophilic attack by means of nitrogen nucleophiles to give 4-alkylidene-23 compounds (M. Kiura et al., Tetrahedron Lett, 1990 31 (30): 4887- 4890, N. Shachat and JJ Bagnell, Jr., J. Org Chem. 1963 28: 991, SJ Miller and R. Tanaka, Nucleophilic Additions to Acetylenes in Selective Organic Transformations, vol.1, BS Thiagarajan (ed.) Wiley &Sons, New York, NY, 1970, p.143) as depicted in Reaction Scheme 4. Propargyl carbinols 21 are prepared by addition of acetylide anions to N-benzyl-4-piperidone. Acetyluride anions are prepared by treatment of a terminal acetylene with a strong base. Typical strong bases include lithium alkyls, lithium dialkylamides, lithium hexane-tildisilazane, and sodium hydride. The reaction is carried out in an aprotic polar solvent such as THF, DME or dioxane at temperatures between -70 and 0 ° C. Cyclization can be carried out by treating the resulting propargyl carbamate with sodium alkoxide in alcohol solvents to give 23. Alternatively, the cyclization can be induced with copper (I) chloride and triethylamine in refluxing THF. The resulting exocyclic olefins 23 (R = CH2Ph) are relatively resistant to hydrogenation under moderate conditions allowing selective removal of the benzyl protecting group to give 23 (R = H) which can be converted to compounds of formula 26 by reductive amination as previously described in Reaction Schemes 1 and 2. Hydrogenolysis at high pressure (1000 psi) reduces the exo-olefins also by removing the benzyl protecting group to give 24 which was converted to piperidines 26 as described previously. REACTION SCHEME 5 Acylation and alkylation of nitriles is achieved by deprotonation of a nitrile with a strong base to form the corresponding stabilized nitrile carbanions. Useful bases for the formation of a-a-cyano carbanions include lithium dialkyl amides, sodium hexamethyldisilazane, sodium or potassium hydride or potassium amide. The reactions are carried out in polar aprotic solvents such as THF, DME and dioxane. The reaction is carried out between -20. and -78 ° C. The addition of the compound N-benzyl piperidin-4-one 10 (R = CH2Ph) to the carbanion derived from the pentane nitrile gives rise to hydroxy nitrile 27.

- (J. March, Adv. Organic Chemistry, John Wiley &Sons, New York, 1992, p. 468-474; S. Arseniyadis et al. Org. Reactions 1984 31: 1-364; H. O. House, Modern Synthetic Reactions, Benjamin Inc, Menlo Park, CA 1972, p. 546-550). The hydroxynitriles can be converted to aminoalcohols by metal hydride reducing agents. (See, RC Larock, Comprehensive Organic Transformations, Verlag Chemie, New York, NY 1989, p.993) Suitable metal hydrides for the reduction of nitriles include the diborane-THF complex, lithium aluminum hydride and diisobutylalum hydride. . The diborane reductions are carried out in ethereal aprotic solvents, especially THF. The reductions of lithium aluminum hydride can be carried out in THF or diethyl ether. The DIBAL reductions are carried out in toluene or THF. DIBAL is available in the form of toluene solutions. The intramolecular cyclization of the aminoalcohol with a phosgene or a phosgene equivalent (eg carbonyl diimidazole) gives rise to carbamate 29. The reaction is carried out in an aprotic solvent in the presence of trialkyl-lamellar base at a temperature between 0- 100 ° C. The rest of the synthesis of the. l-oxa3,9-diaza-spiro [5.5] undecan-2-one compounds of the present invention, including N-alkylation, deprotection of the piperidinyl nitrogen and reductive amination with a suitable N-derivative of 4-oxopiperidine, is carried performed using processes analogous to those described in Reaction Schemes 1 and 2 for l-oxa-3,8-diaza-spiro [4.5] decan-2-ones.

REACTION SCHEME 6 32 The benzo-fused compounds of l-oxa-3,9-diaza-spiro [5.5] undecan-2-one are prepared through the treatment of the compound 10 a-aminoalkoxycarbonyl aryl metalate with an N-protected 4-oxo-piperidine adequate (Reaction scheme 6). The aminoalkoxycarbonyl radical directs the metallation of the aryl ring regiospecifically to the heteroatom (for analogous metalation of aminoacyl aryl compounds see, H. Takai et al., Chem. Pharm. Bull. 1985 33 (3): 1129-39; W. Fuhrer and HN Geschwend, J. Org. Chem. 1979 44: 113-36) to give an intermediate alkoxycarbonyl aminoalcohol compound which cyclizes spontaneously to give 4,4-disubstituted 1,4-dihydro-benzo [d] [1, 3] oxazin-2-one 33. The remainder of the synthesis of the benzofused compounds of l-oxa-3, 9-diaza-spiro [5.5] undecan-2-one of the present invention, including N- alkylation, deprotection of the piperidinyl nitrogens and reductive alkylation with a suitable 4-oxopiperidine N-derivative 10, is carried out using processes analogous to those described in reaction schemes 1 and 2 for l-oxa-3, 8 -diaza-spiro [4.5] decan-2-ones.

REACTION SCHEME 7 3Bü 8b Isomer - S Isomer -R The 4-Butyl-2-oxo-l-oxa-3,8-diaza-spiro [4.5] decane-8-carboxylic acid benzyl ester (12) contains an asymmetric carbon and is therefore a mixture of two .enantiomers. The separation of the diastereomers was carried out by acylation of 12 with (-) -camphanic acid and separating the resulting diastereomers 38a and 38b which exhibit different physical properties and can be separated by conventional methods such as silica gel chromatography, fractional crystallization, and high pressure liquid chromatography (Reaction Scheme 7). The diastereomeric campanic amides were hydrolyzed with hydroxide. of lithium to give rise to 39a and 39b which were obtained as previously described. The compounds of the present invention can be formulated in a wide variety of forms, vehicles and oral administration doses. Oral administration may be in the form of tablets, coated tablets, dragees, hard or soft gelatin capsules, solutions, emulsions, syrups, or suspensions. The compounds of the present invention are effective when administered by other routes of administration including continuous topical (intravenous drip), intramuscular, intravenous, subcutaneous, transdermal parenteral (which may include penetration of an enhancing agent), buccal, nasal, inhalation. and administration of suppositories, among other administration routes. The preferred administration form is generally oral using a daily dose regimen that can be adjusted according to the degree of affliction and the patient's response to the active ingredient. A compound or compounds of the present invention, as well as their pharmaceutically usable salts, together with one or more conventional excipients, carriers, or diluents, may be put in the form of pharmaceutical compositions and dosage units. The pharmaceutical compositions and dosage units may contain conventional ingredients in conventional proportions, with or without additional active compounds or principles, and the dosage unit forms may contain any suitable effective amount of the active ingredient proportional to the daily dose range provided for The pharmaceutical compositions can be employed as solids, such as tablets or filled capsules, semisolids, powders, sustained release formulations, or liquids such as solutions, suspensions, emulsions, elixirs, or filled capsules for oral use, or in the form of suppositories for rectal or vaginal administration, or in the form of sterile injectable solutions for parenteral use. from about 5% to about 95% active compound or compounds (weight / weight). The term "preparation" or "dosage form" includes both liquid and solid formulations of the active compound and those skilled in the art will appreciate that an active ingredient can exist in different preparations depending on the target organ or tissue and the desired dose as well as the pharmacokinetic parameters. The term "excipient" as used herein refers to the compound that is useful for the preparation of a pharmaceutical composition, generally safe, non-toxic, biologically or otherwise undesirable, and includes excipients that are acceptable for veterinary use as well as for human pharmaceutical use. The term "excipient" as used herein includes one or more excipients. Solid form preparations include powders, tablets, pills, capsules, suppositories, and dispersible granules. A solid carrier may be one or more substances which may also act as diluents, flavoring agents, lubricants, suspending agents, preservatives, tablet disintegrating agents, or a material for encapsulation. In the powders, the carrier is generally a finely ground solid that is mixed with the finely ground active component. In tablets, the active component is generally mixed, in appropriate proportion, with a vehicle having the necessary binding capacity and compacted with the desired shape and size. Suitable carriers include, but are not limited to, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, - waxes with low melting point, cocoa butter, and the like. The solid form preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. Liquid formulations are also suitable for oral administration and include emulsions, syrups, elixirs, aqueous solutions, and aqueous suspensions. These include solid forms that are provided to be converted to liquid forms shortly before their administration. The emulsions can be prepared in solutions, for example, in aqueous solutions of propylene glycol or they can contain emulsifying agents such as lecithin, sorbitan monooleate, or acacia. Aqueous solutions can be prepared by dissolving the active component in water and adding suitable colorants, flavors, and stabilizing and thickening agents. Aqueous suspensions may be prepared by dispersing the finely ground active component in water with viscous materials, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents. The compounds of the present invention can be formulated for parenteral administration (eg, by injection, bolus injection or continuous infusion) and can be presented in the form of unit dose ampoules, pre-filled syringes, small volume infusion or in containers multidose with an added preservative. The compositions can be presented in the form of suspensions, solutions, or emulsions in oleic or aqueous vehicles, for example solutions in aqueous polyethylene glycol. Examples of oleic or non-aqueous carriers, diluents, solvents or vehicles include propylene glycol, polyethylene glycol, vegetable oils (eg, olive oil), and injectable organic esters (eg, ethyl oleate), and may contain formulatory agents as preservatives. , humectants, emulsifiers or suspensors, stabilizers and / or dispersants. Alternatively, the active ingredient may be in the form of a powder, obtained by aseptic isolation of a sterile solid or by lyophilization of a solution for constitution with a suitable vehicle before use, for example, with sterile, pyrogen-free water. The compounds of the present invention can be formulated for topical administration in the epidermis as ointments, creams or lotions, or as transdermal patches. Ointments and creams can, for example, be formulated with an aqueous or oleic base with the addition of a suitable thickening and / or gelling agent. Lotions can be formulated with an aqueous or oleic base and, in general, also contain one or more emulsifying agents, stabilizers, dispersants, suspensors, thickeners, and colorants. Formulations suitable for topical administration in the mouth include lozenges containing active agents in a flavored base, usually sucrose and acacia or tragacanth.; pills containing the active ingredient in an inert base such as gelatin and glycerin or sucrose and acacia; and mouthwashes containing the active ingredient -10 in a suitable liquid vehicle. The compounds of the present invention can be formulated for administration as suppositories. A wax with a low melting point, such as a mixture of fatty acids glycerides or cocoa butter is previously melted and The active component is dispersed in it homogeneously, for example, by stirring. The molten homogeneous mixture is then deposited in molds of suitable size, and cooling is allowed to solidify. The compounds of the present invention can be formulated for vaginal administration. Ovules, tampons, creams, gels, pastes, foams or sprays containing the active ingredient together with the appropriate carriers in this type of application. The compounds of the present invention can be formulated for nasal administration. The solutions or suspensions are applied directly in the nostril by conventional means, for example, with droppers, pipettes or atomizers. The formulations can be supplied in simple or multi-dose form. In the case of an eyedropper or a pipette, this can be achieved by administering a predetermined adequate volume of the solution or suspension. In the case of atomizers, this can be achieved, for example, by means of a spray atomizer pump with counter. The compounds of the present invention can be formulated for aerosol administration, particularly intended for the respiratory tract and including intranasal administration. The compound will generally be a particle of small size, for example of the order of five (5) microns or less. This particle size can be obtained by means known for such a purpose, for example by micronization. The active ingredient is provided in a pressurized container with a suitable propellant such as a chlorofluorocarbon (CFC), for example, dichlorodifluoromethane, trichlorofluoromethane, or dichlorotetrafluoroethane, or carbon dioxide or other suitable gas. The aerosol may also conveniently contain a surfactant such as lecithin. The dose of drug administered can be controlled by means of a valve with counter. Alternatively, the active ingredients may be provided in the form of a dry powder, for example a powder mixture of the compound in a suitable powder base such as lactose, starch, hydroxypropylmethyl cellulose and polyvinylpyrrolidine (PVP). The carrier powder will form a gel in the nasal cavity. The powder composition can be presented in the form of single doses, for example in capsules or cartridges of, for example, gelatin or blister packs of which the powder can be administered by means of an inhaler. When desired, the formulations can be prepared with "enteric coatings adapted for sustained or controlled release of the active ingredient, For example, the compounds of the present invention can be formulated in the form of drug delivery mechanisms transdermally or subcutaneously. These release mechanisms are advantageous when a sustained release of the compound is necessary and when strict adherence to the treatment is crucial Compounds in transdermal delivery systems are often attached to a solid skin-adhesive support. combined with a penetration enhancer, for example, Azona (l-dodecylaza-cycloheptan-2-one) .The sustained release systems are inserted subcutaneously into the subdermal layer by means of surgery or injection.The subdermal implants encapsulate the Composed in a liposoluble membrane, for example, silicon a, or a biodegradable polymer, for example, polylactic acid. Suitable formulations with pharmaceutical carriers, diluents and excipients are described in Remington: The Science and Practice of Pharmacy 1995, edited by W. W. Martin, Mack Publishing Company, 191 edition, Easton, Pennsylvania. Skilled scientists in formulation can modify the formulations shown in the specification to provide numerous formulations for a particular route of administration without compromising or destabilizing the therapeutic activity of the compositions of the present invention. The modification of the present compounds to make them more soluble in water or other vehicles, for example, can be easily carried out through small modifications (salt formulation, esterification, etc.), which are well known in this field. It is also customary to modify the route of administration and the dose regimen of a particular compound in order to direct the pharmacokinetics of the present compounds towards a maximum beneficial effect in patients. The term "therapeutically effective amount" as used herein indicates the amount required to reduce the symptoms of the disease in an individual. The dose will be adjusted to the requirements of the individual in each particular case. This dosage can vary with wide limits depending on numerous factors such as the severity of the disease to be treated, the age and general state of health of the patient, other medications with which the patient may be being treated, the route or form of administration and the preferences and experience of the physician involved. For oral administration, a daily dosage of between about 0.01 and about 100 mg / kg of body weight per day should be suitable for monotherapy and / or combination therapy. A preferred daily dosage is between about 0.1 and about 500 mg / kg of body weight, more preferably between 0.1 and about 100 mg / kg of body weight and still more preferable between 1.0 and about 10 mg / kg of weight body per day. Thus, for administration to a 70 kg person, the dosage range will be between 7 mg and 0.7 g per day. The daily dosage can be administered as a single dose or in divided doses, usually between 1 and 5 doses per day. Generally, treatment starts at small doses lower than the optimum dose of the compound. Thereafter, the dose is increased by small increments until the optimum effect is reached for the patient. Those who habitually treat the diseases described herein will be able, without undue experimentation and without dependence on personal knowledge, experience and disclosures of this application, to establish therapeutically effective amounts of the compounds of the present invention for a particular disease and a certain patient. In embodiments of the invention, the active compound or salt can be administered in combination with another antiviral agent, such as a nucleoside reverse transcriptase inhibitor, another non-nucleoside reverse transcriptase inhibitor or an HIV protease inhibitor. When the active compound or its derivatives or salts are administered in combination with another antiviral agent the activity can be increased above that of the original compound. When, the treatment is a combination therapy, the administration may be concurrent or sequential with respect to that of the nucleoside derivatives. "concurrent administration" as used herein includes the administration of agents at the same time or at different times. The administration of two or more agents at the same time can be achieved by means of a simple formulation containing two or more active ingredients or by a substantially simultaneous administration of two or more dosage forms with a single active agent. It should be understood that the references indicated here about the treatment extend both to prophylaxis and treatment of existing conditions, and that the treatment of animals includes the treatment of humans as well as other animals. In addition, the treatment of HIV infection, as used herein, also includes the treatment or prophylaxis of a disease or condition associated or mediated by HIV infection, or the clinical symptoms thereof. The pharmaceutical preparations are preferably in the form of unit doses. In such forms, the preparation is subdivided into unit doses containing suitable amounts of the active component. The unit dosage form can be a packaged preparation, the package contains discrete quantities of the preparation, as well as packed tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, or lozenge, or it can be the appropriate number of any of these packaged forms. The compounds of the present invention can be made by a variety of methods described in the illustrative synthetic reaction schemes shown and described below. The starting materials and reagents used for the preparation of these compounds are available from commercial suppliers, such as Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art following procedures shown in references such as Fieser and Fieser. 's Reagents of Organic Synthesis; Wiley & Sons: New York, Volumes 1-21; R. C. La- Rock, Comprehensive Organic Transformations, 2nd Edition Wiley-VCH, New York 1999; Comprehensive Organic Synthesis, B. Trost and 1. Fleming (Eds.) Vol. 1-9 Pergamon, Oxparad, 1991; Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees (Eds) Pergamon, Oxford 1984, vol. 1-9; Comprehensive Heterocyclic Chemistry II, A. R. Katritzky and C. W. Rees (Eds) Pergamon, Oxford 1996, vol. 1-11; and Organic Reactions, Wiley & Sons: New York, 1991, Volumes 1-40. The following synthetic reaction reaction schemes are merely illustrative of some methods by means of which the compounds of the present invention can be synthesized, and various modifications of these synthetic reaction reaction schemes can be made and will be suggested to those skilled in the art. matter that relates to the disclosure contained in this Application. The starting materials and intermediates of the synthetic reaction reaction schemes can be isolated and purified if desired by conventional techniques, including but not limited to filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectrum data. Unless specified otherwise, the reactions described herein are preferably carried out in an inert atmosphere at atmospheric pressure at a reaction temperature range between about -78 ° C and about 150 ° C, more preferably from about 0 ° C to about 125 ° C, and more preferably and conveniently at room temperature, for example, around 20 ° C. Some of the compounds in the following reaction schemes may be represented by generalized substituents; however, those skilled in the art will appreciate immediately that the nature of the R groups can be varied to give rise to several compounds contemplated in this invention. In addition, the conditions of reaction are alternatives and alternative conditions are well known. The following examples (infra) are given so that those skilled in the art can clearly understand and practice the present invention. They should not be considered as limiting the scope of the invention, they are merely illustrative and representative of it. EXAMPLE 1 4-Butyl-3-cyclohexyJLmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one (1-1) Stage 1: 4- (1-Carboxy-pentyl) -4-hydroxy-piperidine-1-carboxylate benzyl ester To a solution of 15 mL (124 mmol) of diisopropyl amine in 90 mL of anhydrous THF at -40 ° C was added dropwise 45 mL (113 mmol) of n-butyl lithium (2.5 M in hexanes) The reaction mixture it was tempered at 0 ° C. A solution of 6.7 ml (62.1 mmol) of hexanoic acid in 60 ml of anhydrous THF was added dropwise. The reaction mixture was stirred at -20 ° C for 20 m. additional The reaction mixture was cooled to -78 ° C. A solution of 15 g (64.3 mmol) of benzyl 4-oxo-l-piperidine carboxylate in 60 ml of anhydrous THF was added dropwise. The reaction mixture was slowly warmed to room temperature for 18 h. The reaction was treated by adding 25 ml of water. The mixture was acidified to pH 2 with 6N HCl. The aqueous phase was extracted three times with EtOAc. The combined organic phase was dried over magnesium sulfate and evaporated under reduced pressure. Toluene was added to the pale, yellowish oil and evaporated under reduced pressure to provide 21.5g (99%) of 4- (1-carboxy-pentyl) -4-hydroxy-piperidine-1-carboxylate benzyl ester: ms [M ] + = 350.

Stage 2: benzyl ester of 4-butyl-2-oxo-l-oxa-3,8-diaza-spiro [4, 5] decane-8-carboxylate To a solution of 27g of 4- (l-carboxy-pentyl) -4-hydroxy-piperidine-l-carboxylate benzyl ester (61.5 mmol) in 500 ml of toluene was added sequentially 20.4 ml of TEA (68.5 mmol) and 14.8 ml of diphenyl phosphoryl azide (68.5 mmol). The reaction mixture was refluxed under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to room temperature and evaporated under reduced pressure. The residue was dissolved in ethyl acetate. The mixture was washed twice with 1N HCl, twice with saturated sodium bicarbonate, and once with brine. The organic phase was dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (1: 5 EtOAc: DCM) to provide 16.2 g (75%) of 4-butyl-2-oxo-l-oxa-3,8-diaza-spiro [4, 5] benzyl decane-8-carboxylate: ms [M] + = 347.

Step 3: benzyl ester of 4-butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diazaspiro [4, 5] decane-8-carboxylate (13t R * CB £; Yes * tí-Bm R "« e-C3HIf > To a solution of 5.0 g of 4-butyl-2-oxo-l-oxa-3,8-diaza-spiro [4,5] decane-8-carboxylate benzyl ester (14.4 mmol) in 50 ml of DMF was added to the solution. added 994 mg of sodium hydride (21.6 mmol, 60% dispersion in mineral oil). The reaction mixture was stirred for five minutes and 2.2 ml of cyclohexylmethyl bromide (15.8 mmol) were then added. The reaction mixture was stirred under nitrogen for 18 h. The reaction mixture was heated at 70 ° C for three h. The reaction mixture was cooled to room temperature and diluted with 500 mL of EtOAc and washed twice with water, once with brine. The organic phases were dried over magnesium sulphate and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel using an elution gradient (10% to 15% EtOAc / DCM) to provide 4.1 g (65%) of 4-butyl-3-cyclohexylmethyl-2-oxo benzyl ester -l-oxa-3, 8-diaza-spiro [4, 5] decane-8-carboxylate: ms [M] + = 443. Step 4: 4-butyl-3-cyclohexylmethyl-l-oxa-3, 8- diaza-spiro [4, E] decane-2-one Palladium on activated carbon (10 mol%, 10% by weight, dry base, type Degussa) was suspended in a solution of 2.07 g (4.7 mmol) of the benzyl ester of 4-butyl-3-cyclohexylmethyl-2-ox-1 -oxa-3, 8-diaza-spiro [4,5] decane-8-carboxylate and 50 ml of EtOH. The reaction mixture was stirred under a hydrogen atmosphere for 18 h. The solution was filtered through a CELITE® filter to remove the catalyst. Evaporation of EtOH under reduced pressure afforded 1.4 g (95%) of 4-butyl-3-cyclohexylmethyl-1-oxa-3,8-diaza-spiro [4, 5] decan-2-one: ms [M] + = 309. Step 5: 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one To a solution of 0. 75 g (2.4 mmol) of 14 (R = n-Bu; R "= c-C5Hn) and 0.59 g (2.55 mmol) of 15 in 30 ml of dichloroethane was added 1.0 ml (3.4 mmol) of titanium isopropoxide (IV) The reaction mixture was stirred at room temperature, After 0.74 g (3.85 mmol) of sodium triacetoxyborohydride was added after stirring and the mixture was stirred continuously at room temperature, after 4 h CELITE® and 15 ml of 2N were added. NaOH was added The mixture was stirred at RT After 0.5 h, the CELITE® was filtered and washed with dichloromethane and the organic phase was separated The organic phase was washed with brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography and eluted with a gradient (50% ethyl acetate / hexane, ethyl acetate, 5% methyl alcohol / ethyl acetate / 0.4% ammonium hydroxide) to provide 0.7 g (56%) of 1- 1 in the form of a white foam EXAMPLE 2 4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-dimethyl-phenyl) -amide. -diaza-spiro [4, 5] dec-8-yl) -4-methyl-piperidine-l-carboxylic acid (1-80) Stage 1: 4- (4-Butyl) -3- cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4, 5] dec-8-yl) -4- butyl tert-butyl ester cyano-piperidine-1-carboxylate '(18: R = Boc; R' = n-Bu; R "= c- To a solution of 14 (R '= n-Bu; R" = c-C5Hn; 2.46 mmol) in 60 ml of dichloromethane was added N-Boc-4-piperidone, (10: R = Boc, 515 mg: 2.58 mmol) at room temperature The stirred reaction was maintained under a nitrogen atmosphere for 30 m Ti (IV) (0-i-Pr) 4 (1 mL, 3.44 mmol) was added to the reaction and the mixture was stirred at room temperature for 12 h and then refluxed for 4 h The reaction mixture was allowed to cool to room temperature and diethylaluminium cyanide (3.8 ml, 3.87 mmol) was added and stirring was continued for another 5 days.The reaction mixture was diluted with 50 ml of dichloromethane and a few drops of IN NaOH were added until the aluminum granulates could be removed by filtration through CELITE® The organic phase ica was extracted under vacuum and the residue was purified by flash chromatography on silica gel (50% EtOAc / hexane to give the title compound (933 mg; 78% theoretical). Step 2: 4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4, 5] dec-8-yl) -4-methyl tert-butyl ester -piperidine-1-carboxylate (19: R = Boc; R '= n-Bu; R "= c- To a solution of 4- (4-butyl- (3-cyclohexylmethyl-2-oxo) tert-butyl ester -l-oxa-3, 8-diaza-spiro [4, 5] dec-8-yl) -4-cyano-piperidine-l-carboxylate (18: R = Boc; R '= n-Bu; R "= c-C5Hn, 700 mg, 1.35 mmol) in 25 ml of low THF, a nitrogen atmosphere was added with methyl magnesium bromide, (1.3 ml, 4.06 mmol, 3.0 M solution in Et20) at room temperature. The reaction was stirred for 24 h.The reaction was treated by the addition of water and EtOAc (1: 1, 100 ml) and filtered through CELITE.RTM .. The organic phase was separated and dried with sodium sulfate, filtered and the solvent was evaporated to give 545 mg (79%) of 19 (R = Boc; R '= n-Bu; Rn = c-C5Hn): ms [M] + = 506.

Step 3: 4-Butyl-3-cyclohexyl-methyl-8- (4-methyl-piperi-din-4-yl) -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one 19b (R = n-Bu; R "= C-C5H11) To a solution of 4- (4-butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza- tert -butyl ester) spiro [4, 5] dec-8-yl) -4-methyl-piperidine-l-carboxylate (19a: R = n -Bu; R "= c- C5H11; 545 mg; 1.07 mmol) in 20 ml of dichloromethane was added 1 ml of THFA at room temperature and refluxed for 3 h, then stirred for 24 h. at room temperature. The dichloromethane solution was washed with 1N NaOH and water (2x50 ml) and brine (50 ml). The organic phase was separated and dried with sodium sulfate, filtered and the solvent was evaporated to give 300 mg (80% theory) of 19b (R = n-Bu; R "= C-C5H11) ms [M] + = 406. Stage 4: 4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro (2,6-dimethyl-phenyl) -amide [4,5] -dec-8-yl) -4-methyl-piperidine-1-carboxylic acid (1-80) A mixture of 2,6-dimethylbenzoic acid (333 mg, 1.47 mmol), HOBT (225 mg, 1.66 mmol) and PS- carbodiimide (610 mg, 196 mmol) in 20 ml of 10% DMF / dichloromethane) was stirred at room temperature After 16 h, a solution of 19b (400 mg, 0.98 mmol; R = n-Bu; R "= c-C5Hn) in 20 ml of DCM was added.The reaction mixture was stirred at room temperature for 48 h.The resulting mixture was filtered through CELITE® and washed with 10% DMF / DCM. evaporated to dryness under reduced pressure and the crude product was purified by flash chromatography on silica gel (25% MeOH / EtOAc) and the resulting amine was converted into the corresponding hydrochloric acid salt with HCl / Et20 to provide 1-80 ( 34.5 mg, 6% theory), ms [M + H] + = 538. EXAMPLE 3 8- (1-Benzenesulfonyl-piperidin-4-yl) -4-butyl-3-cyclohexylmethyl-1-oxa-3, 8-diaza-spiro [4, 5] decan-2-one (1-71) To a solution of 19b (R = n-Bu; Ru = c-C5Hn; l.Og; 2.24 mmol), TEA (0.311 mL, 0.226 g, 2.24 mmol) and 25 mL of Et20 was added 1.79 g of toluenesulfonyl chloride (9.78 mmol). The reaction mixture was stirred at room temperature for 18 h. The solid triethylammonium chloride was filtered and the volatile solvents were evaporated in vacuo. The residue was partitioned between EtOAc and IN NaOH. The organic phase was washed with water and brine, dried over magnesium sulfate, and evaporated to give 1-71. The crude product was purified by flash chromatography on silica gel.

EXAMPLE 4 4-Butylidene-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diazaspiro [4, 5] decan-2- ona (1-14) Stage 1: l-Benzyl-4-pent-l-inyl-piperidin-4-ol To a solution of 5.47 g (80.3 mmol) of 1-pentyne in 65 ml of THF at -78 ° C were added 32.1 ml of n-butyl lithium (80.3 mmol; 2.5M in hexanes). After the addition was complete, the reaction mixture was warmed to 0 ° C and a solution of 8.44 g (44.6 mmol) of 1-benzyl-4-piperidone and 40 ml of THF was added dropwise. The cooling bath was removed and the reaction mixture was stirred at room temperature. After 17 h, the reaction was treated by the addition of saturated ammonium chloride and diluted with EtOAc. The aqueous phase was extracted twice with EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate and evaporated to obtain a reddish gold colored oil. The crude product was purified by flash chromatography on silica gel (EtOAc / hexane 1: 1 65:35). The pale gold oil was dried over sodium sulfate to provide 8.91 g (78%) of l-benzyl-4-pentynyl-4-piperidinol: ms (ESI) [M + H] + = 258. step 2: 8- Benzyl-4-butylidene-3-cyclohexylmethyl-l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one RH-fl-CsHjiJ To a solution of 21 (R = Bn; R '= n-Pr; 1.43 g (5.56 mmol) in 25 ml of toluene was added 9.8 ml of potassium t-amylate (16.68 mmol; 1.7 M in toluene). The mixture was heated to 50 ° C and a solution of 851 mg (6.11 mmol) of cyclohexylmethyl isocyanate (J. Med. Chem. 1996 39: 1157-1163) in 6 ml of toluene was added. The reaction was heated at 70 ° C for 17 h, treated with saturated ammonium chloride and diluted with ethyl acetate. The aqueous phase was washed twice with EtOAc and the combined organic phases were washed with brine, dried over sodium sulfate and evaporated to give a yellow oil. The crude product was purified by flash chromatography on silica gel (25:75 EtOAc / hexane) to give 190 mg (9%) of 23 (R = Bn; R '= n-Pr; R "= c-C5Hp) in form of an unstable pale yellow oil: ms (ESI) [M + H] + = 397. Stage 3: 4-butylidene-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidine -4-yl] -l-oxa-3, 8-diazaspiro [4, 5] decan-2-one (1-14) The removal of the benzyl protecting group from 23 (R = Bn; R '= n-Pr; R "= c-C5Hn) was achieved by catalytic hydrogenolysis in the presence of 20% Pd (0H) 2 / C and EtOH a about 40 psi The final step was carried out as described in step 5 of Example 1. The title compound (1-14) was obtained as a clear crystal (3%): MS (ESI) m / z [M + H] + 522. EXAMPLE 5 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4- (2-methoxy-ethyl) -l -oxa-3, 8-diazaspiro [4,5] decan-2-one (1-12) Stage 1: l-Benzyl-4- (3-methoxy-prop-1-ynyl) -piperidin-4-ol To a solution of 4.67 g (66.6 mmol) of 3-methoxypropine in 50 ml THF at -78 ° C was added 26.7 ml of n-butyl lithium (66.6 mmol, 2.5 M in hexanes). After completing the addition, the reaction mixture was warmed to 0 ° C and a solution of 7.01 g (37.0 mmol) of 1-benzyl-4-piperidone and 35 ml of THF were added dropwise. The cooling bath was removed and the reaction mixture was stirred at room temperature. After 18 h, the reaction was treated with saturated ammonium chloride and diluted with water and EtOAc. The aqueous phase was washed with EtOAc and the combined organic phases were washed sequentially with water and brine. The EtOAc was dried over sodium sulfate, filtered and evaporated in vacuo to give a reddish gold colored oil. The crude product was purified by flash chromatography on silica gel eluting with EtOAc / hexanes (8: 2). The gold-colored oil was dried to give 8.30 g (86%) of 21 (R = Bn; R '= CH2OMe): ms (ESI) [M + H] + = 260. Step 2: 8-Benzyl-3-cyclohexylmethyl-4- [2-methoxy-et- (Z) -lidene] -l-oxa- 3, 8-diaza-spiro [4.5] decan-2-one To a solution of 220 mg (0.85 mmol) of 21 (R = Bn; R '= CH2OMe) dissolved in 10 ml of toluene was added 1.2 ml of ~ t- potassium amylate (1.88 mmol; 1.7 M in toluene). The mixture was heated to 75 ° C and a solution of cyclohexylmethyl isocyanate (22: R = c-.C5Hu, 186 mg, 1.88 mmol) in 3 ml of toluene was added. The reaction was heated at 75 ° C for 17 h, treated with water and diluted with ethyl acetate. The phases were separated and the aqueous phase was washed twice with EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo to give a gold-colored oil. The crude product was purified by flash chromatography on silica gel and eluted with a EtOAc / hexanes gradient (1: 1 - 7: 3) to give 100 mg (29%) of 23 (R = Bn; R '= CH2OMe; R "= C-C5H11) in the form of pale yellow oil: ms (ESI) [M + H] + 399. Step 3: 3-Cyclohexylmethyl-4- (2-methoxy-ethyl) -l-oxa-3 , 8-diaza-spiro [4,5] decan-2-one t W-2OUm «« ^? ct) To a solution of 500 mg (1.25 mmol) of 21 (R = Bn; R '= CH2OMe) in 15 ml of EtOH was added 200 mg of 20% Pd (OH) 2 in carbon and 5 drops of HC10. The mixture was pressurized to 1000 psi of H2 in a steel reactor pump and stirred at room temperature for 17 h. The reaction was filtered over CELITE® and the filter pellet was washed with EtOH. The filtrate was evaporated in vacuo and the residue was partitioned between 1M NaOH and EtOAc. The organic phase was washed sequentially with water and brine, dried over sodium sulfate and evaporated in vacuo to provide 268 mg (69% theory) of 24 (R '= CH20Me; R "= C-C5H11) as an yellow color: ms (ESI) [M + H] + = 311.

Stage 4 -. 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl-J-piperidin-4-yl] -4- (2-methoxy-ethyl) -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one (2S; R '= CH, 0Mc; u = c.C <H «» Rw = 2,6-di-Me-benzoyl Reductive amination was carried out as described in step 5 of example 1. The crude product was purified by flash chromatography eluting with a gradient of methylene chloride / ethanol (45: 2-45: 4) to provide 46 mg (10% theory) of 1-12 in the form of a transparent crystal: ms (ESI) (M + H) + = 526. EXAMPLE 6 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) - piperidin-4-yl] -4-ethoxymethyl-l-oxa-3,8-diazaspiro [4, 5] decan-2-one (I-11) Step 1: 8-Benzyl-3-cyclohexylmethyl-4-methylene-1-oxa-3,8-diazaspiro [4, 5] decan-2-one The title compound was prepared in 57% yield using a procedure described in step 2 of example 3 but substituting l-benzyl-4-ethynyl-piperidin-4-ol (21: R = Bn; R '= H; JJDeVoss, J. Med. Chem. 1994 37 (5): 665) by l-benzyl-4-pent-1-ynyl-piperidin-4-ol. The crude product was purified by flash chromatography eluting with EtOAc / hexane (1: 1) to provide 23 (R = Bn, R '= H; R "= c-C5H11) as a yellow syrup: ms (ESI) ) [M + H] + = 355. Step 2: 8-Benzyl-3-cyclohexylmethyl-4-hydroxymethyl-l-oxa-3,8-diaza-spiro [4.5] decan-2-one To a solution of 2.0 g (5.64 mmol) of 23 (R = Bn; R '= H; R "= C-C5H11) in 100 mL of THF was added 2.75 g (11.28 mmol) of 9-BBN and the reaction was refluxed for 2 h.The reaction was cooled to 0 ° C and 30 ml of 1M NaOH was added followed by a slow addition of 40 ml of 30% H202.The mixture was stirred at room temperature for 1.5 h, put into A mixture of ice and water was treated with 1M Na 2 SO 3 The crude mixture was diluted with EtOAc and the aqueous phase was washed twice with EtOAc The combined organic extracts were washed twice with 1M Na 2 SO 3 then with water and brine. Organic was dried over sodium sulfate, filtered and concentrated in vacuo to give a yellowish oil.The crude product was purified by gel flash chromatography on silica gel eluting with EtOAc / hexanes (85:15) followed by methylene chloride / methanol (9: 1) to provide 2.9 g of impure 50a (R "= c-C5Hn) in the form of a thick gold-colored syrup: ms (ESI) (M + H) + = 373. Step 3: 3-Cyclohexylmethyl-4-hydroxymethyl-l-oxa-3,8-diaza-spiro [4.5] decan-2-one C5fc = HRw = • - &C ^ iu) To a solution of 24a (R = Bn; R '= OH; R "= c-05Hn; 2.0 g (5.37 mmol) in 20 ml of EtOH was added 200 mg of 20% Pd (OH) 2 on carbon. The mixture was stirred under the pressure of a balloon of H2 at room temperature for 3.5 d. The reaction was filtered through celite® and the filter pellet was washed with EtOH. The solvent was evaporated in vacuo and dried residue to give 1.52 g (100%) of 50c (R "= c-C5Hn) in the form of a yellow syrup: ms (ESI) (M + H) + = 283.

Step 4: tert-butyl ester of cyclohexylmethyl-4-hydroxymethyl-2-oxo-l-oxa3, 8-diaza- "spiro [4, 5] decane-8-carboxylate rxx C? p - To a solution of 50c (R "= c-C5H ??; 1.52 g; 5.37 mmol) in 20 ml of MeOH and 10 ml of 1M NaOH was added (Boc) 20 (1.17 g; 5.37 mmol ) and the reaction was stirred at room temperature for 21 h.The reaction was reduced in volume and diluted with water and EtOAc The aqueous phase was extracted in aqueous phase twice with EtOAc The combined organic phases were washed sequentially with water and brine, dried over sodium sulfate and concentrated in vacuo to give a yellow oil.The crude product was purified by flash chromatography on silica gel eluting with a gradient of EtOAc / hexane (1: 1.7: 3) to give 650 mg (32%) of 50b (Rn = C-C5H11) in the form of a colorless glass: ms (ESI) (M + H) + = 383.

Step 5: 3-Cyclohexylmethyl-4-ethoxymethyl-2-oxo-l-oxa3, 8-diaza-spiro [4, 5] decane-8-carboxylate tert-butyl ester To a suspension of NaH (25 mg, 0.62 mmol, 60% NaH in mineral oil) in 5 mL of THF was added a solution of 50b (Ru = c-C5Ha ?; 217 mg, 0.57 mmol) and 10 mL of THF. After 15 minutes, ethyl iodide (97 mg, 0.62 mmol) was added and the reaction was stirred at room temperature for 2.5 d. The reaction was treated with water and diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted twice with EtOAc. The combined organic phases were sequentially washed with water and brine, dried over sodium sulfate and concentrated in vacuo to give a yellow oil. The crude product was purified by flash chromatography on silica gel eluting with EtOAc / hexane (1: 1) to give 157 mg (67%) of 51c (R "= C-C5H11) as a colorless crystal: ms (ESI) ) (M + H) + = 411.

Step 6: 3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) piperidin-4-yl] -4-ethoxymethyl-l-oxa-3,8-diazaspiro [4, 5] decan-2- ona 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-ethoxymethyl-l-oxa-3,8-diaza-spiro [4,5] decan-2- ona (I-11) was obtained from 51c c-C5Hn) using the procedures of step 3 of example 2 and step 5 of example 1. The crude product was purified by flash chromatography on silica gel eluting with a gradient of sodium chloride. methylen / MeOH (90: 1 - »90: 4) to give 189 mg (95% theory) of 1-11 as a colorless oil: ms (ESI) (M + H) + = 526. EXAMPLE 7 5-Butyl-3-cyclohexylmethyl-9- (2,6-dimethyl-benzoyl) -1-oxa-3,9-diaza-spiro [5,5] undecan-2-one (1-76) Step 1: 2- (l-Benzyl-4-hydroxy-piperidin-4-yl) -hexane-nitrile To a solution of 10 g, 12.4 mmol of hexanonitrile in 100 ml of THF at -78 ° C was added n-BuLi (41.2 ml, 103 mmol of 2.5 M in hexane) dropwise over 10 m. After 4 h the reaction was placed in a mixture of saturated NH 4 Cl, extracted with EtOAc, the combined EtOAc extracts were washed with brine and the organic phase was dried over sodium sulfate. After filtration the solvents were removed in vacuo and the crude residue was purified by flash chromatography on silica gel using an elution gradient of (10-50% EtOAc / hexane) to give 15.7 g of 27 (R '= n-Bu ) in the form of orange oil (53% theory). Step 2: 9-benzyl-5-butyl-l-oxa-3, 9-diaza-spiro [5, 5] -undecan-2-one (R '= n-Bu) in 100 ml of THF was added lithium aluminum hydride (52.4 ml, 52.4 mmol, 1.0 M LAH in THF). After lh the reaction is treated by the addition of 2 ml of water, 2 ml of 2N NaOH and 6 ml of water with stirring. The reaction was stirred for 30 m then filtered and the filtrate was washed with EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate and evaporated to dryness. The crude product was taken up in 60 mL of THF and carbonyldiimidazole (17 g, 104.7 mmol) was added. After stirring for 48 h, the reaction mixture was placed in brine, the organic phase was separated, dried over sodium sulfate and concentrated to dryness. The residue was purified by flash chromatography on silica gel eluting with a gradient (50% EtOAc / hexane to -1% MeOH / EtOAc) to give 2.3 g of pure 29 (R '= Bu) together with 9 g. of product. partially purified. Step 3 9-Benzyl-5-butyl-3-cyclohexylmethyl-1-oxa-3, 9-diaza-spiro [5,5] undecan-2-one To a solution of 27 (R '= n-Bu, 1.8 g, 19 mmol) in 30 ml of NMP was added NaH (0.27 g, 6.8 mmol) The reaction was stirred at room temperature After 30 minutes, cyclohexylmethyl bromide (1.2 ml, 8.5 mmol) The reaction mixture was heated at 80 ° C for 16 h, cooled to room temperature and the reaction mixture was placed in brine, the organic phase was separated, dried over sodium sulfate. and concentrated to dryness The residue was purified by flash chromatography on silica gel eluting with a gradient (10-50% acetone / hexane) to give 30 (R '= n-Bu; Rfl = c-C5Hn; 1.5 g; 65% theory) Stage 4: 5-Butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one A mixture of 30 (R '= n-Bu; R "= c-C5Hu; 1.5 g, 3.6 mmol), 0.24 g Pd (OH) 2 and 2 ammonium formate (3 g, 36.4 mmol) in 30 ml of EtOH it was heated to reflux.After 3 h, 10 ml of 10% aqueous ammonium hydroxide was added and the mixture was refluxed after refluxing. The reaction mixture was cooled to room temperature, filtered through CELITE®, washed with EtOH, was concentrated to dryness and the residue was purified by flash chromatography on silica gel with a gradient (EtOAc at 20% NeOH / EtOAc containing 0.4% NH 4 OH) to give 30 (R '= n-Bu; R "= c- C5Hu; 0.92g, 79% theory) in the form of a transparent oil. The final product 1-76 was prepared by treating the piperidine 30 (R '= n-Bu; R "= c-C5Hn) as described in step 5 of Example 1. EXAMPLE 8 Step 1 (4-fluorophenyl) carbamate tert-butyl ester To a solution of 25 ml of p-fluoroaniline (264 mmol) in 400 ml of anhydrous THF was added 59.3 g of di-tert-butyl dicarbonate (272 mmol) in three servings The reaction mixture was kept under a nitrogen atmosphere and heated to reflux for 3 hours. The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The residue was dissolved in 300 ml of EtOAc. The organic phase was washed sequentially with 2N HCl and brine, dried over sodium sulfate and the solvent was evaporated in vacuo. The solid was recrystallized from boiling hexanes to provide 47.4 g (85% theory) of (4-fluorophenyl) carbamate (10) tert-butyl ester: ms M + = 212. Step 2: tert-butyl ester of spiro acid [6-fluoro-4H-3, l-benzoxazine-4, 4'-piperidin] -2 (1H) -one-carbamate To a solution of tert-butyl ester of (4-fluoro-phenyl) carbamate (16. Og; 75.8 mmol) in 300 ml of anhydrous THF at -78 ° C was added tert-butyl lithium dropwise at a sufficient rate. to keep the internal temperature below -75 ° C. The reaction mixture was stirred at -78 ° C for 30 m. additional The reaction mixture was warmed to -25 ° C and stirred for two h. The reaction mixture was re-cooled to -78 ° C and a solution of 15.1 g of 4-oxo-piperidine-1-carboxylate (75.8 mmol) in 160 ml of anhydrous THF was added dropwise. The reaction mixture was stirred at -78 ° C for four h. A solution of 1 ml of potassium tert-butoxide (1.0 M in tetrahydrofuran) was added. The reaction mixture was allowed to warm to room temperature slowly over a period of 18 h. The crude mixture was diluted with 300 ml of Et20 and the organic phase was washed sequentially with 2N HCl, water and brine. The organic phase was dried over sodium sulfate and concentrated in vacuo. The residue was triturated with EtOAc to provide 10.61 g (42%) of spiro [4H-3, l-benzoxazine4,4'-piperidine] -2 (1H) -one-BOC (33) as a solid: ms M + = 337. Stage 3: tert-butyl ester of 4-cyclohexylmethyl-spiro [6-fluoro-4H-3, l-benzoxazine-4, 4'-piperidine] -2 (ÍH) -one-carbamate To a solution of 2.0 g of 33 (5.9 mmol) in 40 ml of DMF was added 492 mg of sodium hydride (10.7 mmol, 60% dispersion in mineral oil). The reaction mixture was stirred for one h and 1.86 ml of cyclohexylmethyl bromide (13.3 mmol) was added dropwise. The reaction mixture was heated at 70 ° C for 18 h, then cooled to room temperature and diluted with 200 ml of water. The mixture was extracted three times with EtOAc. The organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (10% EtOAc / hexanes) to provide 1.21 g (47%) of 34 (R "= C-C5H11): ms M + = 433.

Step 4: 3-cyclohexylmethyl-spiro [4H-3, 1-6-fluorobenzoxazine-4, 4'-piperidine] -2 (1H) -one To a solution of 1.2 g of 34 (R "- = c-C5Hn, 2.8 mmol) in 10 ml of dichloromethane was added 10 ml of THFA.The reaction mixture was stirred under a nitrogen atmosphere for 18 hours. extracted under pressure reduced to provide the trifluoroacetic acid salt of 35 (R "= c-C5H11) The trifluoroacetate salt was dissolved in 20 ml of dichloromethane and 20 ml of saturated aqueous sodium bicarbonate were added.The reaction mixture was stirred for 20 m after which 40 ml of dichloromethane was added The organic phase was separated and the aqueous phase was extracted with dichloromethane The combined organic phases were dried over sodium sulfate and concentrated in vacuo to provide 918 mg (99%) of (R "= C-C5-H11): ms M + = 333. Reductive amination with N- (2, 6-dimethylbenzoyl) -4-piperidone to provide 1-414 was carried out as described in step 5 of Example 1 EXAMPLE 9 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) - piperidin-4-yl] -3- (2-methoxy-ethyl) -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid (1-81) 12 R ^ H; RI, * & .BU 41 CEjCOjff Step 1: 4-Butyl-l-oxa-3,8-diazaspiro [4, 5] decane-2-one 2.0 g (5.8 mmol) of 4-butyl-2-oxo-l-oxa-3 benzyl ester , 8-diazaspiro [4, 5] decane-8-carboxylate 12 (R = CBZ; R '= n-Bu) was dissolved in 25 ml of EtOH and Pd / C (10 mol%, 10% by weight, dry base, type Degussa). The reaction mixture was stirred under a hydrogen atmosphere for 18 h. The solution was filtered through a pad of celite® and washed twice with EtOH. Evaporation of the combined filtrate and washes under reduced pressure afforded 1.09 g (88%) of 4-butyl-l-oxa-3,8-diaza-spiro- [4,5] decane-2-one 12 (R = H; R '= n-Bu): ms [M] + = 213.

Step 2: 4-Butyl-8- [1- (2,6-dimethyl-benzoylYpiperidinyl-4-yl] -l-oxa-3,8-diaza-spiro [4.5] decan-2-one A a solution of 4-butyl-l-oxa-3,8-diaza-spiro [4, 5] decane-2-one (12: R = H; R '= n-Bu; 1.09 g; 5.1 mmol)) in 30 ml of DCM was added 1.24 g (5.4 mmol) of 1- (2,6-dimethylbenzoyl) -piperidin-4-one followed by 2.1 ml (7.1 mmol) of Ti (IV) (0-i-Pr). The reaction mixture was stirred under nitrogen for 18 h. Sodium triacetoxyborohydride (1.6 g: 7.7 mmol) was added to the reaction mixture followed by glacial HOAc (0.365 ml, 6.4 mmol). The reaction mixture was stirred for 24 h. Aqueous ammonia (20 ml, 10% aqueous solution) was added and the solution was stirred for an additional 10 min. The mixture was filtered by gravity through a ChemElute ™ cartridge. The organic phases were evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel with gradient elution (2% to 10% methanol in ethyl acetate with 0.4% ammonia) to provide 1.6 g (73%) of 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decane-2-one: ms [ M] + = 428. Step 3: 5-Butyl-3- (2-methoxyethyl) -9- [2- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9 -diaza-spiro [5, 4] decan-2-one To a solution of 21 mg (0.05 mmol) of 4-butyl-8- [1- (2,6-dimethyl-l-benzoyl) -piperidin-4- il] -l-oxa-3, 8-diazaspiro [4, 5] decane-2-one dissolved in 1 ml of dry 1,4-dioxanes in a test tube with a screw cap was added 100 mg of 10% KF in alumina and 7.1 μl (.075 mmol) of 2-bromoethylmethyl ether. The tube was sealed and heated at 110 ° C for 18 h. The reaction was filtered through CELITE® and the filter pad was washed with methylene chloride (3 X .5 ml). The combined filtrate and washings were concentrated under reduced pressure. The residue was then purified using reverse phase semi-preparative HPLC in Aquisil with elution gradient (10% -90% acetonitrile / .1% THFA aqueous buffer) which gave 16 mg (52%) of 1-81 as salt of triflouroacetate. EXAMPLE 10 Resolution of Enantiomers Separate diastereomers 11 33 Step 1 To a solution of 600 mg (1.73 mmol) of 12 (R = Z; R1, n-Bu) in 10 ml of THF at -78 ° C was added n-BuLi (0.70 ml, 1.90 mmol; hexanes). The reaction mixture was stirred at -78 ° C for 30 min followed by dropwise addition of (ÍS) (-) - campanic acid chloride (412 mg, 1.90 mmol) dissolved in 3 ml of THF. The reaction mixture was stirred -78 ° C for 15 min, then at room temperature during 4 h. The reaction was treated with saturated ammonium chloride and diluted with EtOAc and water. The phases were separated and the aqueous phase was extracted three times with EtOAc. The combined organic extracts were washed sequentially with saturated NaHCO3, water and brine, dried over sodium sulfate and evaporated to give a gold-colored oil. The diastereomers (38a and 38b) were separated by flash chromatography eluting with a gradient of hexane / EtOAc (8: 2 to 7: 3) to provide 150 mg (16%) of the most non-polar isomer was isolated as a thick oil colorless: ms (ESI) [M + H] + = 527. A second fraction of 210 mg (23%) of the less non-polar isomer was isolated as a white crystalline solid: ms (ESI) [M + H] ] + = 527. Step 2 To a solution of 210 mg (0.40 mmol) of 38a or 38b from step 1 in 6 ml of THF and 2 ml of water at 0 ° C was added LiOH monohydrate (36 mg; 0.86 mmol). After stirring at 0 ° C for 2 h, the THF was removed and the residue was diluted with saturated NaHCO 3 and ether. The phases were separated and the aqueous phase was extracted twice with ether. The combined extracts were washed with brine, dried over sodium sulfate and evaporated to give an off-white powder which was dried in vacuo to provide 135 mg (97%) of the carbamate 39: ms (ESI) [M + H] + = 347. The resolved oxazolinones 39a and 39b are converted to (R) - and (S) -I1 as described in Example 1. EXAMPLE 11 Human CCR5 ligand-receptor binding assay protocol The human CCR5 receptor ( Genebank ID: 29169292) was cloned into a mammalian expression vector, pTarget (Promega). The construct was transfected into CHO-Gai6 cells using a Fugene reagent (Roche). The clones were selected under conditions of antibiotic pressure (G418 and Hygromycin) and were classified 4 times with a cell sorter that activates the fluorescence and a monoclonal antibody specific for the CCR5 receptor (BD Biosciences Farmigen, Mab 2D7, Cat. No. 555993 ). The clone with the highest expression (100,000 copies per cell) was chosen for the binding assays. Adherent cells in a 225 ml tissue culture flask (~90% confluence) were cultured using 1 mM EDTA in PBS (phosphate buffer solution) without Ca2 + and Mg2 +. Cells were washed twice with PBS without containing Ca2 + and Mg2A The CHO-Gai6-hCCR5 cells were then resuspended (lxl06 / ml) in an ice-cold binding buffer (50 mM HEPES, 1 mM CaCl2, 5 mM MgCl2, 0.5% BSA, 0.05% NaN3, pH 7.24), pH 7.4), supplemented with 0.5% fresh BSA and 0.05% NaN3. Eighty μl of CHO-Ga? 6-hCCR5 cells (lxl06 / ml) were added to 96-well plates. All dilutions were made in binding buffer (50 mM HEPES, 1 mM CaCli, 5 mM MgCl2, 0.5% BSA, 0.05% NaN3, pH 7.24). The plates were incubated in a cell agitator at room temperature for 2 h at a final concentration of 0.1 nM 125IRAN or 125IMIP-la or 125I MlP-lβ. The dilutions of the compound were made in PBS, 1% BSA. The total reaction volume was 100 μl per well. The compounds to be tested were added to the cells before the addition of radioligand. After incubation, the cells were grown on GF / C filter plates using a Packard cell cultivator. The filters were pretreated with 0.3% PEI /0.2% BSA for 30 min. The filter plate was washed 5 times rapidly with 25 mM HEPES, 500 mM NaCl, 1 mM CaCl 2 and 5 mM MgCl 2 adjusting the pH to 7.1. The plates were dried in an oven (70 ° C) for 20 min, 40 μl of scintillation fluid was added and sealed with Packard TopSeal-A. The Packard Top Count was used to measure radioactivity for 1 min per well. The total binding was determined with control wells with radioisotope and buffer and the non-specific binding was determined using an excess of cold RANTES at some control wells.

The specific binding was determined by subtracting the nonspecific signal from the total binding. The results are expressed as the percentage of specific bindingRRANTS. The IC50 values were determined using various concentrations of the ligand to be tested in triplicate and the data was analyzed using a GrafPad Prism (GrafPad, San Diego, CA). Some exemplary IC50 data resulting from the human CCR5 ligand-receptor binding assay are shown below: Do not . Compound Union IC50 (μM) RANTES Mip-la Mip-lb 1-1 0.014 0.018 0.013 1-3 0.14 0.14 0.27 1-73 0.2 0.4 0.9 1-75 0.0045 0.0034 0.04 Example 12 Cell-cell fusion assay mediated by the HIV envelope The compounds were tested in a cell-cell fusion induced reporter luciferase activity. One of the cell lines used (effector cells) was derived from Hela cells overexpressing the tat-HIVl and HIV-1 gpl60 protein from an R5 virus. The second cell line (target cells) is CEM-NKr-CCR5-luc that constitutively expresses CD4 and the CCR5 co-receptor. The Diana cell also carries a cassette for expression of the luciferase gene driven by HIV-1 LTR. When the effector and the cells When the target is co-cultured, the gpl60 protein expressed on the surface of the effector cell recognizes its CD4 and CCR5 receptors in the target cells and initiates the fusion of the two cell types. Such a protein activates the expression of the luciferase gene under the control of HIV LTR elements (response-tat) carried out by the target cells. The ability of CCR5 antagonists to block cell-cell fusion was monitored by measuring the decrease in luciferase activity. The reagents used for the assays were prepared as follows 1) Hela-R5-16 cell (monolayer): A stable HeLa tet-on cell line (BD Bioscience, Cat #: 630901) carrying pTRE2-Hig-gpl60 to express HIV gpl60 after induction Dox and pTat-GFP to express the fusion protein HIV Tat-GFP. Cells were maintained in DMEM + 10% FBS + 400 ppt / ml G418 + 200 Itg / mL Hygromycin B. Cells were diluted twice at 1:10. 2) CEM-NKr-CCR5-Luc cell (suspension): A cell line derived from lymphocytes from the USA NIH AIDS Reagents Program. (Ref #: 5198) which expresses human CD4 and CCR5 and carries a luciferase reporter gene driven by HIV LTR. The cells were maintained in RPMI 1640 + 10% FBS + 4 mM glutamine + 0.8 mg / mL G418. Cells were divided twice a week at 1:10 to maintain good activity. 3) The Steady-Glo luciferase assay system: Promega, Cat #: E2550; stored at -80 ° C in aliquots after being dissolved with the buffer provided. 4) . Doxycycline (Dox): BD Bioscience, Cat #: 8634-1; diluted to "2 mg / ml solution stoc in water and stored at -20 ° C. The tests were carried out as follows: Day 1: Hela-R5-16 cells were separated with 1 x trypsin (0.25%), arranged in 7,500 cells per well in white plates of cell culture in 384 wells in 25 μl of phenol supplemented with DMEM free of red with 10% FBS and 1 μg / ml of Dox Day 2: Ten μl, of compounds diluted in phenol were added RPMI-1640 red-free containing 5% DMSO (final conc DMSO = 1% in assays.) Fifteen μl of CEM-NKr-CCR5-Luc cells were added in RPMI-1640 phenol free of red containing 10% FBS medium ( 15,000 cells / well) Day 3: Fifteen of SteadyGlo substrate was added per well, leaving it under vigorous stirring at room temperature for 60 min, the luciferase activity was read in a top-counter or luminometer. (Experimental controls: CCR5 antagonist control standard, no control compound, no target cell control.) Some IC50 data from Examples resulting from the HIV cell-mediated cell-cell fusion assay are given below: EXAMPLE 13 FORMULATIONS Pharmaceutical compositions of the subject compounds during administration by several routes were prepared as described in this Example. Composition for Oral Administration (A) Ingredients% p./p. Active ingredient 20.0% Lactose 79.5% Magnesium stearate 0.5% The ingredients are mixed and dispensed in capsules containing about 100 mg each; One capsule would be approximately the total daily dose. Composition for Oral Administration (B) Ingredients% p./p. Active ingredient 20.0% Magnesium stearate 0.5% Croscarmellose sodium 2.0% Lactose 76.5% PVP (polyvinylpyrrolidine) 1.0% The ingredients are combined and granulated using a solvent such as methanol. The formulation is then dried and packed into tablets (containing about 20 mg of active compound) with an appropriate compression machine.

Composition for Oral Administration (C) Ingredients% p./p. Active Compound 1.0 g Fumaric acid 0.5 g Sodium chloride _ 2.0 g Methyl paraben 0.15 g Propyl paraben • 0.05 g Granulated sugar 25.5 g Sorbitol (70% solution) 12.85 g Veegum K (Vanderbilt Co.) 1.0 g Aromas - 0.035 ml Dyes 0.5 mg Distilled water cs up to 100 ml The ingredients are mixed to form a suspension for oral administration. Parenteral Formulation (D) Ingredient% p./p. Active ingredient 0.25 g Sodium chloride cs to make it isotonic Water for injections to 100 ml The active ingredient is dissolved in a portion of water for injections. A sufficient amount of sodium chloride is then added with stirring to make the solution isotonic. The solution is made to be weighed with the rest of the water for injections, filtered through a 0.2 micron membrane filter and packed under sterile conditions. Formulation of Suppositories (E) Ingredient "% p./p. Active Ingredient 1.0% Polyethylene glycol 1000 74.5% Polyethylene glycol 4000 24.5% The ingredients are melted together and mixed in a steam bath, and put into the molds containing 2.5 g of total weight. Topical formulation (F) Ingredients grams Active compound 0.2-2 Span 60 2 Tween 60 2 Mineral oil 5 Petrolatum 10 Methyl paraben 0.15 Propyl paraben 0.05 SHA (hydroxybutyl anisole) 0.01 Water q.s. 100 All ingredients, except water, were combined and heated to about 60 ° C with agitation. A sufficient amount of water of about 60 ° C is then added by vigorous stirring to emulsify the ingredients, and then water q.s. up to around 100 g. Nasal Spray Formulations (G) Several aqueous suspensions containing 0.025-0.5 percent are prepared as nasal spray formulations. The formulations optionally contain inactive ingredients such as, for example, microcrystalline cellulose, sodium carboxymethyl cellulose, dextrose, and the like. It can be added - hydrochloric acid to adjust the pH. The nasal spray formulations can be distributed by a nasal spray with a measuring pulsator that distributes around 50-100 microliters of formulation per action. A typical dose scale is 2-4 sprays every 4-12 hours. The features disclosed in the following description, or the following claims, expressed in their specific forms or in terms of an average for the performance of the disclosed function, or a method or procedure for achieving the disclosed result, as appropriate, may, separately, or in any combination of such characteristics, it can be used to carry out the invention in the various forms thereof. The following invention has been described in some details by way of illustration and example, for purposes of clarity and understanding. It will be obvious to those skilled in the field that changes and modifications may be put into practice, within the scope of the indexed claims. Therefore, it should be understood that the foregoing description is intended to be illustrative and not restrictive. The scope of the invention should, therefore, be determined not with reference to the previous description, but it should be determined in reference to. the following indexed claims, throughout the total scope of the equivalents to which these claims refer. All patents, patent applications and publications cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent that each individual patent, patent application or publication is thus individually denoted. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (17)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A compound according to formula I, characterized because: A is (CH2) q; R1 is C (= 0) R4, S (0) pR, or C (= 0) X, wherein X is NR5R6 or OR11; R2a and R2b are (a), independently hydrogen, C? _10 alkyl, C2_? Or alkenyl, C? -10 haloalkyl, C3_7 cycloalkyl, C3_7 cycloalkyl-C? _3 alkyl, C? _? Or heteroalkyl, C? -? alkylidene, C? -? or heteroalkylidene, aryl, aryl-C? _3 alkyl, heteroaryl, heteroaryl-C? _3 alkyl, C? _? 0 alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -O- , -S-, -NH- or -NR5-, - (CH2) WR8 where w is an integer between 2 and 6, and the C2_6 alkyl chain optionally contains a double bond, - (CH2) WCH = NR9 where w is an integer between 2 and 6; or (b), together with the carbon atoms to which they are attached, are o-phenylene optionally substituted with 1 to 3 substituents independently selected from the group consisting of C? -s alkyl, C? _6 haloalkyl, C? 6 alkoxy, C? -e thioalkyl, C? _ Alkylsulfonyl, halogen, NR5? R6 ?, cyano and nitro with the proviso that if R2a, R2b, together with the carbon atoms to which they are attached are optionally substituted or phenylene, m is 1; R3 is C? -? Or alkyl, C2_? Or alkenyl, Ci -io heteroalkyl, C3-7 cycloalkyl, C? _6 C3-7 alkyl cycloalkyl, C? _6 heterocyclic alkyl, aryl, aryl-C? _3 alkyl, heteroaryl C, C6 alkyl heteroaryl, C (= 0) R3a wherein R3a is C? -10 alkyl, C2-? Or alkenyl or C3_7 cycloalkyl, or a fragment of formula Ila-IIc; R4 is C? _? Or alkyl, C3_ cycloalkyl-C? -? Or substituted alkyl, heterocycle, aryl, or heteroaryl; R5 and R6 are (a) H, C? -1Q alkyl, C? _ Or heteroalkyl, C3_7 cycloalkyl, C? _6 alkyl, C3_7 cycloalkyl, C? _6 heterocyclic alkyl, aryl, aryl-C? _3 alkyl, heteroaryl, or C6-alkyl heteroaryl when considered independently; or (b) C3_6 alkylene or [(CH2) 2] 20 when considered together; R5a and R6a are (a) hydrogen, C6-6alkyl or C6-6alkylcarbonyl when considered independently or (b) C3_6alkylene or [(CH2) 2] 0 when considered together; R7 is hydrogen, cyano or? -e alkyl; R8 is -CN, -N02, -CONR5aRSa, COR9, "NHS02C1_6 alkyl, R9 is OH or C? -e alkoxy, R10 is N or N + -OA R11 is C? -? Or alkyl, -Ci-ioheteroalkyl, C3 - cycloalkyl, C? _6 alkyl-Ca_ cycloalkyl, heterocycle-Ci-g alkyl, aryl, aryl-C? alkyl, heteroaryl, C? -6 alkyl heteroaryl, m is 0 or 1; n is independently from 0 to 2 or is independently 0 or 1, p is 0 to 2, q is 1 to 3, wherein each of the aforementioned heteroaryls is independently selected from the group consisting of pyridyl, 1-oxy-pyridinyl, pyrimidyl, oxypyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl indolinyl, N-Boc-indolinyl, quinolinyl, isoquinolinyl, benzofuranyl, 4,5,6,7-tetrahydrobenzofuranyl and 1, 2, 3 , 4-tetrahydroacridinyl, each of said aryls and heteroaryls are optionally independently substituted by 1 to 3 substituents selected from the group consisting of hydroxyl, C? _6 alkyl, C? -5 haloalkyl, C? -6 alkoxy, C? _6 haloalkoxy, C? _6 thioalkyl, aryl, aryl C? _3 alkyl, aryloxy, heteroaryloxy, thioaryl, thioheteroaryl, aryl C? _ 3 alkoxy, heteroaryl; heterocyclyl, C? -s alkyl heterocycle, C? -6 alkylsulfonyl, -N? S02C? _6 alkyl, S02NR5aR6a, (CH2) UC02R9, (CH2) uCONR5aR6a, -XxC (= 0) X2, C? _ or alkylcarbonyl, halogen, NR5aR6a, cyano, nitro and C? _? 0 alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -O-, -S-, -NH- or NR5, where u is an integer of 0 to 6, X1 is NR5b or O; X2 is NR5R6 or OR3 and R5b is H or C? _6 alkyl; each of the aforementioned heterocycles is independently selected from the group consisting of pyrrolidinyl, 1-methyl-pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, tetrahydrofuranyl, dioxolanyl and pyranyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxy C6-6 alkyl , C? -and haloalkyl, C? -6 alkoxy,? -β thioalkyl, C? _6 alkylsulfonyl, halogen, NR5aR6a 'cyano and nitro; pure enantiomers, partially resolved enantiomers, racemic mixtures, pharmaceutically acceptable acid addition salts, hydrates and solvates thereof.
2. 2. The compound according to claim 1 characterized in that it has the formula or Ib, tt wherein: R2a and R2b are (A), independently hydrogen, C? -? 0 alkyl, Ci-ao haloalkyl, C3_7 cycloalkyl, C3_ cycloalkyl-C? _3 alkyl, C? -? Or heteroalkyl, C? _? 0 alkylidene, Ca -io heteroalkylidene, - (CH2) qR8, aryl, aryl-C? _3 alkyl, heteroaryl, heteroaryl-C? _3 alkyl, Cj-? or alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -O-, -S-, -NH- or -NR5-, or (B), together with the carbon atoms to which they are attached are o-phenylene optionally substituted with 1 to 3 substituents independently selected from the group consisting of-β alkyl, C? _6 haloalkyl, C? _6 alkoxy, C? -β thioalkyl, C6-alkylsulfonyl, halogen, NR5aR6a, cyano and nitro with the proviso that if R2a, R2b, together with the carbon atoms to which they are attached, are optionally substituted o-phenylene, m is 1; R3 is Ci-alkyl, C? _? Heteroalkyl, C3_7 cycloalkyl, C? -6 C3_7 alkyl cycloalkyl, heterocycle C? _6 alkyl, aryl, aryl-C? Alkyl, heteroaryl, C? _6 alkyl heteroaryl; A, X, R1, R5, R6, R5a, R6a, R7, R8, R9, R10, R11, m, n, o, p, q, are as defined in (i). wherein, - each of the aforementioned heteroaryls are independently selected from the group consisting of pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl and isothiazolyl, each of said aryl and heteroaryls are optionally substituted independently with 1 to 3 substituents selected from the group consisting of hydroxyl, C? -6 alkyl, C? _ haloalkyl, C? _6 alkoxy, C? -s thioalkyl,? -e alkylsulfonyl, halogen, NR5aR6a cyano and nitro; each of said heterocycle are independently selected from the group consisting of pyrrolidinyl, 1-methyl-pyrrolidinyl; piperidinyl, tetrahydrofuranyl, and pyranyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl, Ci-β alkyl, C ?6 haloalkyl, C?-6 alkoxy, C ?6 thioalkyl, C ?6 alkylsulfonyl, halogen, NR5aR6a, cyano and nitro.
3. 3. The compound according to claim 1, characterized in that it has the formula le, wherein R1 is C (= 0) R4, S (0) pR4, or C (= 0) X, wherein X is NR5R6 or OR11; R2a is C? -? Or alkyl, C? _? Or haloalkyl, C3_7 cycloalkyl, C3_7 cycloalkyl-C? _3 alkyl, C? _10 heteroalkyl, C? -? Or alkylidene, C? -? Or heteroalkylidene or C? _? or alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -OR-, -S-, -NH- or -NR5-; R2b is hydrogen; R3 is C? -? Or alkyl, C3_7 cycloalkyl, C? _6 alkyl-C3_7 cycloalkyl, optionally substituted aryl, optionally substituted aryl-C? _3 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-C? _3 alkyl; R4 is C? -? Or alkyl, optionally substituted aryl, optionally substituted heteroaryl; R7 is hydrogen, or C? _6 alkyl; m is O or 1; p is 2; X, R5, R6 and R11 are as defined in claim 1.
4. 4. The compound according to claim 3, characterized in that R7 is hydrogen or methyl.
5. 5. The compound according to claim 3, characterized in that R1 is COR4; R2 is C? _? Or alkyl, C? _? Or heteroalkyl or C? _? 0 alkyl • wherein 2 or 3 carbon atoms not adjacent to the alkyl chain can be optionally substituted independently with -O-, - S-, -NH- or -NR5-; R 4 is optionally substituted aryl or optionally substituted heteroaryl.
6. 6. The compound according to claim 5, characterized in that R4 is optionally substituted aryl.
7. 7. The compound according to claim 6, characterized in that R 4 is optionally substituted phenyl.
8. 8. The compound according to claim 5, characterized in that R4 is optionally substituted heteroaryl.
9. 9. The compound according to claim 8, characterized in that R4 is optionally substituted pyridyl, optionally substituted pyrimidyl, optionally substituted pyrazolyl, optionally substituted oxazolyl, optionally substituted isoxazolyl or optionally substituted pyrrolyl.
10. 10. The compound according to claim 1, characterized in that it has the formula Id where A is (CH2) q; R2a is C? -? Or alkyl, C? _? 0 haloalkyl, C3_7 cycloalkyl, C3_7 cycloalkyl-C? _3 alkyl, C? _ Or heteroalkyl, C? _? 0 alkylidene, C? -? Or heteroalkylidene or C? _? Or alkyl wherein 2 or 3 non-adjacent carbon atoms are independently substituted with -OR-, -S-, -NH- or NR5; R3 is C? -? Or alkyl, Ci -io heteroalkyl, C3-cycloalkyl, C -s alkyl C3_ cycloalkyl, heterocycle C? -6 alkyl, aryl, aryl-C? -3 alkyl, heteroaryl, heteroaryl-C? -3 I rent; R 4 is optionally substituted aryl or optionally substituted heteroaryl; R7 is hydrogen or Ci-e alkyl; q is from 1 to 3. The compound according to claim 10, characterized in that A is (CH2) 2. 12. The compound according to claim 1 with the formula characterized in that R2 and R2b together with the carbon atoms to which they are attached are ortho-phenylene, optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl, C? _6 alkyl, C? _6 haloalkyl, C? _6 alkoxy, C6-thioalkyl, C6-6 alkylsulfonyl, halogen, NR5aRda, cyano and nitro; R3 is C? -? Or alkyl, C3_7 cycloalkyl, C? _5 alkyl-C3_7 cycloalkyl, optionally substituted aryl, optionally substituted aryl-C? _3 alkyl, optionally substituted heteroaryl, and optionally substituted heteroaryl-C? _3 alkyl; R 4 is optionally substituted aryl or optionally substituted heteroaryl; R5 and R6a are (A) hydrogen, C? -6 alkyl or Ci-β alkylcarbonyl when they are considered independently or (B) C3_6 alkylene or [(CH2) 2] 20 when considered together; R7 is hydrogen or C6-6 alkyl. The compound according to claim 1, characterized in that it is 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 8-diaza -spiro [4,5] decan-2-one 3-Benzyl-4-butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -1-oxa-3,8-diaza- spiro [4, 5] decan-2-one 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydro-pyran-4-ylmethyl) -l -oxa-3, 8-diazaspiro [4, 5] decan-2-one 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-isobutyl-l- oxa-3, 8-diaza-spiro [4.5] decan-2-one 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydro- furan-3-ylmethyl) -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with hydrochloric acid 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-propyl-l-oxa-3,8-diaza-spiro [4,5] decan-2-one 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-isobutyl-l-oxa-3,8-diaza-spiro [4,5 ] -decan-2-one 4-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -pi? eridin-4-yl] -l-oxa-3,8-diaza-spiro [4,5 ] decan-2-one 3-Butyl-4-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-ethoxymethyl-l-oxa-3,8-diaza-spiro [4 , 5] decan-2-one 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4- (2-methoxy-ethyl) -l-oxa-3, 8-diazaspiro [4, 5] decan-2-one 3-Cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -4- (2-methoxy-ethyl) -l -oxa-3, 8-diazaspiro [4, 5] decan-2-one; compound with hydrochloric acid 4-But- (E) -ylidene-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 8-diaza- spiro [4, 5] decan-2-one 4-butyl-3-cyclohexylmethyl-8- [8- (2,6-dimethyl-benzoyl) -8-azabicyclo [3.2.1] oct-3- il] -l-oxa-3, 8-diazaspiro [4.5] decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [8- (2,6-dimethyl-benzoyl) -8-aza -bicyclo [3,2,1] oct-3-yl] -l-oxa-3,8-diazaspiro [4.5] decan-2-one 4-butyl-3-cyclohexylmethyl-8- [1- (4 , 6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro [4.5] decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (2,4-dimethyl-pyridine-3-carbonyl) -piperidin-4-11] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one 4-Butyl-3 -cyclohexylmethyl-8- [1- (2-methyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4.5] decan-2-one 4-Butyl-3- cyclohexylmethyl-8- [1- (1, 3, 5-trimethyl-lH-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (4-methoxy-2,6-dimethyl-benz oil) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2, 4-dimethyl-6-oxo-6H-pyran-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3,5-dimethyl-isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] -decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethoxy-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3-fluoro-2-methyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4 , 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,3-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] ] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,4-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5 ] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (l-methyl-lH-pyrrole-2-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro [4,5] decan2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (lH-pyrrole-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] ] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-ethyl-5-methyl-2H-pyrazole-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 8 -diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-methylamino-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-dimethylamino-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-difluoro-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan-2-one; compound with trifluoroacetic acid 8- [1- (l-Acetyl-piperidine-4-carbonyl) -piperidin-4-yl] -4-butyl-3-cyclohexylmethyl-l-oxa-3, 8-diaza-spiro [4, 5] decan2-one; compound with trifluoroacetic acid 8- (l-Benzoyl-piperidin-4-yl) -4-butyl-3-cyclohexylmethyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 8-diaza-spiro [4, 5] dec-8-i1) -piperidine-1-carbonyl ] -benzonitrile; compound with trifluoroacetic acid 4-Butyl-8- (l-cyclohexanecarbonyl-piperidin-4-yl) -3-cyclohexylmethyl-l-oxa-3,8-diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (furan-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (furan-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (pyridine-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan- 2-one; compound with trifluoroacetic acid 3- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4,5] -de.c-8-yl) -piperidine acid -1-carbonyl] -benzoic acid; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-trifluoromethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (5-methoxy-lH-indole-2-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro [ 4, 5] decan2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (5-methyl-thiophene-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (thiophene-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (pyridine-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-methyl-pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3-methyl-furan-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (pyrazine-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2-chloro-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3,8-diaza-spiro [4,5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (5-methyl-isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-methyl-thiazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (l-methyl-lH-pyrazole-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (l-methyl-lH-imidazole-2-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (tetrahydro-furan-2-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro [4, 5] decan-2- ona; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-methoxy-thiophene-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3-methyl-pyridine-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (lH-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] decan-2 ~ ona; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8-. { 1- [2- (1-methyl-1H-imidazol-4-yl) -acetyl] -piperidin-4-yl} -l-oxa-3, 8-diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- (1-phenylacetyl-piperidin-4-yl) -1-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-imidazol-1-ylacetyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3-morpholin-4-ylpropionyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] -decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8-. { l- [3- (4-Methyl-piperazin-1-yl) -propionyl] -piperidin-4-yl} -l-oxa-3, 8-diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-lH-tetrazol-5-ylacetyl) -piperidin-4-yl] -l-oxa-3,8-diaza-espyro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3-pyridin-3-ylpropionyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] -decan-2-one; compound with trifluoroacetic acid 4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4, 5] dec-8-yl) -pip "eridin-1-carboxylate of benzyl 4-Butyl-3-cyclohexylmethyl-8- [1- (3,5-dimethyl-isoxazole-4-sulfonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro- [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (5-chloro-l, 3-dimethyl-lH-pyrazole-4-sulfonyl) -piperidin-4-11] -3- cyclohexylmethyl-l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa- 3, 8-diaza-spiro [4, 5] dec-8-yl) -piperidine-1-sulfonyl] -2,5-dimethyl-furan-3-carboxylate methyl; compound with trifluoroacetic acid 8- (1-Benzenesulfonyl) -piperidin-4-yl) -4-butyl-3-cyclohexylmethyl-l-oxa-3, 8-diaza-spiro [4.5] decan-2-one, compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl- 8- [1- (thiophene-2-sulfonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,4,6-trimethyl-benzenesulfonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan- 2- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4,5] dec-8 2-one (2, 6-dimethyl-phenyl) -amide -yl) - piperidine-1-carboxylic acid; compound with trifluoroacetic acid l-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -1,4,9-triaza-spiro [5, 5] undecano- 2, 5-dione l-Butyl-3- ((S) -cyclohexyl-hydroxy-methyl-1) -9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -1,4 , 9-triazaspiro [5, 5] undecane-2, 5-dione (mp 246.9-248) 5-Butyl-3-methyl-9-. { l- [(E) -3- (3, 4, 5-trimethoxy-phenyl) -acyloyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5,5] -undecan-2-one; compound with trifluoroacetic acid (2,6-dimethyl-phenyl) -amide of 4- (5-butyl-3-methyl-2-oxo-l-oxa-3,9-diaza-spiro [5, 5] undec acid) 9-yl) -piperi-dine-1-carboxylic acid; compound with trifluoroacetic acid 8- [1- (2,6-Dimethyl-benzoyl) -piperidin-4-yl] -3-phenethyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2 ona; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with hydrochloric acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methoxy-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-ethyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound methane 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-phenethyl-1-oxa-3,8-diaza-spiro [4, 5] decan -2-ona; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-fluoro-ethyl) -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-hexyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -pi? eridin-4-yl] -3- ((S) -2-methyl-butyl) -l-oxa- 3, 8-diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (3-methyl-butyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclopropylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (5-methyl-hexyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-ethyl-butyl) -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-.phi- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-pentyl-l-oxa-3,8-diaza-spiro [4,5] ] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methyl-benzyl) -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3- (2-cyclohexyl-ethyl) -8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-fluoro-benzyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (1-phenyl-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclobutylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-hydroxy-ethyl) -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-hydroxy-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 8- [1- (2,6- 'Dimethyl-benzoyl) -piperidin-4-yl] -4-methyl-3- (tetrahydro-furan-2-ylmethyl) -l-oxa-3, 8 -diaza-spiro [4,5] -decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-hydroxy-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-hydroxy-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methoxy-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 8- [1- (2,6-Dimethyl-benzoyl) -piperidin-4-yl] -4-methyl-3- (tetrahydro-furan-2-ylmethyl) -l-oxa-3, 8- diaza-spiro [4.5] -decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (4-fluoro-2-trifluoromethyl-benzyl) -l-oxa-3, 8-diaza-spiro- [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-trifluoromethyl-benzyl) -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3- (2,6-difluoro-benzyl) -8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 8- diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3- (2-diethylamino-ethyl) -8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methoxy-ethyl) -l-oxa-3,8-diaza -spiro [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-propyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 3, 4-Dibutyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -1-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-pyridin-3-ylmethyl-l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 2-. { 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,8-diaza-spiro [4, 5] dec-3- ilmetil} methyl -furan-3-carboxylate; compound with trifluoroacetic acid 2-. { 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,8-diaza-spiro [4,5] dec-3- il} -N, N-diethylacetamide; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methoxy-benzyl) -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-pyridin-4-ylmethyl-l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-pyridin-2-ylmethyl-l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3- (2-dimethylamino-ethyl) -8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-morpholin-4-yl-ethyl) -l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-piperidin-1-yl-ethyl) -l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-pyrrolidin-1-yl-ethyl) -l-oxa-3, 8-diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- [2- (1-methyl-pyrrolidin-2-yl) -ethyl] - l-oxa-3,8-diazaspiro [4, 5] decan-2-one; compound with trifluoroacetic acid 2-. { 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,8-diaza-spiro [4, 5] dec-3- il} -N, N-dimethylacetamide; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methyl-thiazol-4-ylmethyl) -l-oxa-3, 8-diaza-spiro [4,5] -decan-2-one; compound with trifluoroacetic acid 3- (2-tert-Butoxy-ethyl) -4-butyl-8- [1- (2,6-dimethyl-benzol) -piperidin-4-yl] -l-oxa-3, 8- diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclopentylmethyl-8 - "[1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5 ] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-4-morpholin-4-yl-benzoyl) -piperidin-4-yl] -l -oxa-3, 8-diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl ] -3-thiazol-4-ylmethyl-l-oxa-3,8-diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2, 6- dimethyl-benzoyl) -piperidin-4-yl] -3- (2-pyrrol-1-yl-ethyl) -l-oxa-3,8-diaza-spiro [4.5] decan-2-one; Trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (4-methyl-pent-3-enyl) -l-oxa-3, 8- diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (1-methyl) -butyl) -l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydrorpyran-2-ylmethyl) -l-oxa-3,8-diaza- spiro [4.5] - decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-ethoxy-ethyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- [2- (2-methoxy-ethoxy) -ethyl] -l-oxa -3, 8-diaza-spiro [4, 5] decan-2-one; composed with. Trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (3,5-dimethyl-isoxazol-4-ylmethyl) -l-oxa-3, 8-diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (5-methyl-isoxazol-3-ylmethyl) -l-oxa-3, 8-diaza-spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (3-methyl-pyridin-2-ylmethyl) -l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (4-fluoro-butyl) -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-fluoro-2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4, 5] dec-8-yl) -piperidine-1-carbonyl ] -3,5-dimethylbenzamide; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-4-pyridin-4-yl-benzoyl) -piperidin-4-yl] -l-oxa-3, 8- diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-9-yl) -piperidine-1- acid carbonyl] -3,5-dimethyl-benzoic acid; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- (1- (2,6-dimethyl-4-pyridin-4-yl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 4- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 9-diaza-spiro [5] , 5] undec-9-yl) -piperidine-1-carbonyl] -3,5-dimethyl-benzoate; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4-iodo-2 , 6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl- 9- [1- (2,6-dimethyl-4-thiophen-2-yl-benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro- [5, 5] undecan-2 -one: compound with trifluoroacetic acid 4- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 9-diaza-spiro [5, 5] undec-9-yl) -piperidine- 1-carbonyl] -3,5-dimethyl-benzonitrile; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-4-pyridin-3-yl-benzoyl) -piperidine- 4-il] -l-oxa-3, 9-diaza-spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [2,6-dimethyl-4- (4-methyl-thiazol-5-yl) -benzoyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid. { 4- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4.5] dec-8-yl) -piperidine-1-carbonyl] -3, 5-difluorophenyl} -butyl tert -butyl carbamate 8- [1- (4-Amino-2,6-difluoro-benzoyl) -piperidin-4-yl] -4-butyl-3-cyclohexylmethyl-l-oxa-3, 8-diaza- spiro [4, 5] decan-2-one N-. { 4- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4.5] dec-8-yl) -piperidine-1-carbonyl] -3, 5-difluoro-phenyl} -acetamide 2- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,8-diaza-spiro [4.5] dec-8-yl) -piperidine-1-carbonyl] - 3-methyl-benzonitrile 2- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 9-diaza-spiro [5, 5] undec-9-yl) -piperidine-1- carbonyl] -3-methyl-benzonitrile 5-But-3-enyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5,5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9- [4-methyl-1- (2,4,5-trimethyl-thiophene-3-carbonyl) -piperidin-4-) il] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9- [4-methyl-1- (5-methyl-3-phenyl- isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9-. { l- [4,6-Dimethyl-2- (pyridin-2-yloxy) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diazaspiro [5,5] ndecan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3,5-dichloro-pyridine-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-'one- (S) -4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3 , 8-diaza-spiro [4, 5] decan-2-one (R) -4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] - l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (3,5-dichloro-pyridine-4-carbonyl) -piperidine- 4-yl] -8-oxi-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) -piperidine -4-yl] -3- (1-hydroxy-cyclohexylmethyl) -l-oxa-3,8-diazaspiro [4, 5] decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (4 -methoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -8-oxy-1-oxa-3, 8-diaza-spiro [4, 5] decan-2-one 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (1-hydroxy-cyclohexylmethyl) -l-oxa-3,9-diazaspiro [5,5] undecan-2-one 5 -Butyl-3-cyclohexanecarbonyl-9- [1- (2,6-dimethyl- benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5,5] undecan-2-one l-. { 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-3 ilmetil} - cyclohexanecarbonitrile (E) -4-. { 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-5- il} -but-2-methyl enoate (E) -4-. { 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-5- il} -but-2-enonitrile 4-. { 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5, 5] undec-5- il} -methylbutyrate 4-. { 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5, 5] undec-5- il} -butyronitrile 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5- ((E) -4-oxo-pent-2-enyl) -l-oxa- 3, 9-diazaspiro [5,5] undecan-2-one Acid (E) -4-. { 3-cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-5- il} -but-2-enoic 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] - 5- ((E) -4-hydroxy-pent-2-enyl) - l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5- ( 4-oxo-pentyl) -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one 4- Acid. { 3-cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-5- il) -butyric 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5- (4-hydroxy-pentyl) -l-oxa-3, 9-diazaspiro [ 5.5] undecan-2-one. { 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-5- il) -acetaldehyde oxime 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5- ((E) -pent-2-enyl) -l-oxa-3 , 9-diazaspiro [5, 5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5-pentyl-l-oxa-3, 9-diazaspiro [5.5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5- ((E) -3-methanesulfonyl- alyl) -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] - 5- (2-methoxy-ethyl) -l-oxa-3,9-diazaspiro [5,5] undecan-2-one 3-Cyclohexylmethyl-9- [2: - (2,6-dimethyl-benzoyl) -piperidine -4-yl] -5- (3-methanesulfonyl-propyl) -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one 5-Allyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, -diaza-spiro [5, 5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2, 6 -dimethyl-benzoyl) -piperidin-4-yl] - 5-propi ll-oxa-3, 9-diazaspiro [5,5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5- (3, 3, 3-trifluoro-2-hydroxy-propyl) -l-oxa3, 9-diaza-spiro [5,5] undecan-2-one 3-Cyclohexylmethyl-9- [1- (2, 6-dimethyl-benzoyl) -piperidin-4-yl] -5- (3, 3,3-trifluoro-2-hydroxy-propyl) -l-oxa3, 9-diaza-spiro [5, 5] undecan-2 -one 3-Cyclohexylmethyl-5- (2-cyclopropyl-ethyl) -9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diazaspiro [5, 5] undecan-2-one 7- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 9-diaza-spiro [5, 5] undec-9-yl) -piperidine- 1-carbonyl] -2, 3-dihydro-indole-1-carboxylic acid tert-butyl ester 5-Butyl-3-cyclohexylmethyl-9- [1- (2,3-dihydro-lH-indole-7-carbonyl) -piperidine -4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one (R) -5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl) benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5,5] undecan-2-one (S) -5-Butyl-3-cyclohexylmethyl-9- [1- ( 2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5,5] undecan-2-one 4-Butyl-3-methyl-8- [1- (2,4,6-trimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dichloro-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with triflufoacetic acid 4-Butyl-8- [1- (2-chloro-6-methyl-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-dichloro-4-methyl-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (4-methoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro- [4, 5Jdecan-2-one; compound with trifluoroacetic acid 8- [1- (4-Butoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-butyl-3-methyl-l-oxa-3, 8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (4-ethoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2-chloro-6-fluoro-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 8- [1- (2-Bromo-6-methyl-benzoyl) -piperidin-4-yl] -4-butyl-3-methyl-l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,6-difluoro-4-methoxy-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-methyl-8- [1- (2,4,6-trimethoxy-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound. ' with trifluoroacetic acid 4-Butyl-8- [1- (2,3-dimethyl-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [4, 5] decan -2-ona; compound with trifluoroacetic acid 4-Butyl-8- [1- (2,4-dimethyl-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (2-dimethylamino-benzoyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-methyl-8- [1- (lH-pyrrole-2-carbonyl) -piperidin-4-yl] -1-oxa-3,8-diaza-spiro [4, 5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (3, 5-dimethyl-isoxazole-4-carbonyl) -piperidin-4-yl] -3-methyl-l-oxa-3, 8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-8- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -3-methyl-l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 8- [l- (4-Butoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-butyl-3-cyclohexylmethyl-l-oxa-3, 8-diaza-spiro [ 4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-hydroxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with hydrochloric acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-ethoxy-2,6-dimethyl-benzoyl) -pi? eridin-4-yl] -l-oxa-3,8-diaza- spiro [4.5] decan-2-one; compound with hydrochloric acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4,6-dimethylpyrimidine-5-carbonyl) -4-methyl-pipridin-4-yl] -l-oxa-3,8-diaza- spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2, 4-dimethyl-pyridine-3-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 8- diaza-spiro- [4, 5] decan-2-one; compound with trifluoroacetic acid 8- [1- (l-Benzyl-3, 5-dimethyl-lH-pyrazole-4-carbonyl) -4-methyl-piperidin-4-yl] -4-butyl-3-cyclohexylmethyl-l- oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3, 5-dimethyl-l-phenyl-lH-pyrazole-4-carbonyl) -4-methyl-piperidin-4-yl] -l- oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dichloro-benzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 8- [1- (4-Benzyloxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-butyl-3-cyclohexylmethyl-l-oxa-3,8-diazaspiro [4] 5] decan-2-one; compound with hydrochloric acid 4-Butyl-3-cyclohexylmethyl-8- [1- (5-methyl-3-phenyl-isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza- spiro- [4,5] decan- 2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3-methyl-thiophene-2-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2-methyl-2H-pyrazole-3-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8 - "[1- (2-methyl-5-propyl-2H-pyrazole-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 8 -diaza-spiro- [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-methyl-2-phenyl-thiazole-5-carbonyl) -piperidine -4-yl] -l-oxa-3, 8-diaza-spiro- [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-methyl -2-pyridin-3-yl-thiazole-5-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spi-ro [4, 5] decan-2-one; compound with acid trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (3, 5-dimethyl-yl-l-pyrrole-2-carbonyl) -piperidin-4-yl] -l-oxa-3, 8-diaza-spiro - [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (5-ethyl-2-methyl-2H-pyrazole-3-carbonyl) -piperidin-4 -yl] -l-oxa-3, 8-diaza-spiro- [4,5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (4-methyl-thiazole -5-carbonyl) - piperidin-4-yl] -l-oxa- 3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,4-dimethyl-thiazole-5-carbonyl) -piperidin-4-yl] -l-oxa-3,8-diaza-spiro [ 4,5] decan-2-one; compound with trifluoroacetic acid 5- [4- (4-Butyl-3-cyclohexylmethyl-2-oxo-oxa-3,8-diaza-spiro [4.5] dec-8-yl) -piperidine-1-acid acid amide carbonyl] -1- methyl-lH-pyrrole-2-sulfonic acid; . compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8-. { 1- [4- (2-methoxy-ethoxy) -2,6-dimethyl-benzoyl] -piperidin-4-yl} -l-oxa-3, 8-diaza-spiro [4, 5] decan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dichloro-benzoyl) -piperidin-4-y1] -l-oxa-3,9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-6-methyl-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dichloro-4-methylbenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4-methoxy-2,6-dimethylbenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 9- [1- (4-Butoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [ 5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4-ethoxy-2,6-dimethylbenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-6-fluoro-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,4,6-trimethylbenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 9- [1- (2-Bromo-6-methyl-benzoyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-difluoro-4-methoxy-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [ 5.5] -undecan-2-one; compound with trifluoroacetic acid 4- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 9-diaza-spiro [5, 5] undec-9-yl) -piperidine-1-carbonyl ] -3,5-dimethyl-benzamide; compound with trifluoroacetic acid 5-Butyl-9- [1- (4-chloro-2-methoxy-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-1-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,3-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5 ] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 4-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methoxy-4-methyl-sulfanyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro- [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-dimethylaminobenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] -undecan-2 -one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3, 5-dimethyl-isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (2-Bromo-6-fluoro-benzoyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (1-Benzyl-3, 5-dimethyl-1H-pyrazole-4-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-1-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (5-Acetyl-2,4-dimethyl-lH-pyrrole-3-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,4,6-trimethoxybenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (3-chloro-2,6-dimethoxy-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [ 5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-fluoro-6-methoxybenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3,6-dichloro-2-methoxybenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethoxy-3-nitro-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro acid [5,5] undecan-2-one trifluoroacetic; 5-Butyl-3-cyclohexylmethyl-9- [1- (2,4,6-trichlorobenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2 -one; compound with trifluoroacetic acid 5-Butyl-9- [1- (3-chloro-2,6-difluoro-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [ 5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-3,6-difluoro-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [ 5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-fluoro-6-trifluoromethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] - undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (6-chloro-2-fluoro-3-methyl-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diazaspiro [ 5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-6-fluoro-3-methyl-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,4,6-trifluorobenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (3-chloro-2-fluoro-6-trifluoromethyl-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza- • spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,3,6-trifluorobenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-6-nitro-benzoyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diazaspiro acid [5, 5] undecan-2-one trifluoroacetic; 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-ethyl-l-oxa-3,9-diaza-spiro [5, 5] undecan-2- dna; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-phenethyl-l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-fluoro-ethyl) -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid. 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- ((S) -2-methyl-butyl) -l-oxa-3, 9-diaza- spiro [5, 5] undecan-2-o? a; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (3-methyl-butyl) -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclopropylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-ethyl-butyl) -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methyl-benzyl) -l-oxa-3, 9-diana-spiro [ 5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3- (2-cyclohexyl-ethyl) -9- [1- (2,6-dimethylbenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [ 5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-fluoro-benzyl) -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclobutylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, -diaza-spiro [5,5] undecan -2-ona; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-methoxy-ethyl) -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-propyl-l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 3,5-Dibutyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -1-oxa-3,9-diaza-spiro [5, 5] undecan- 2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-pyridin-4-ylmethyl-l-oxa-3, 9-diaza-spiro [ 5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3- (2-dimethylamino-ethyl) -9- [1- (2,6-dimethylbenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [ 5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-morpholin-4-yl-ethyl) -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (2-piperidin-1-yl-ethyl) -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclopentylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; "compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydro-pyran-4-ylmethyl) -l-oxa-3, 9 -diaza-spiro [5, 5] - undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3-pyridin- 3-ylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidine -4-yl] -3- pyridin-2-ylmethyl-l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- ( 2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydro-furan-2-ylmethyl) -l-oxa-3,9-diaza-spiro [5,5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- [1,3] dioxolan-2-ylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydro) -piran-2-ylmethyl) -l-oxa-3, 9-diaza-espi ro [5, 5] - undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 4-dimethyl-pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] - undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,4,5-trimethyl-thiophene-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza- spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -3- (tetrahydro-furan-3-ylmethyl) -l-oxa-3, 9- diaza-spiro [5,5] -undecan ~ 2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (6-hydroxy-2,4-dimethyl-pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-espi-ro [5, 5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (4-Amino-2,6-difluoro-benzoyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [ 5, 5] undecan2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methoxy-4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4-fluoro-2,6-dimethylbenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 4-dimethyl-l-oxy-pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9 acid -diaza-spiro [5, 5] undecan-2-one trifluoroacetic; 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-methylsulfanyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-l-oxy-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9 acid -diaza-spiro [5,5] undecan-2-one-trifluoroacetic; 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 3-dihydro-lH-indole-7-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (5-methyl-3-phenyl-isoxazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { l- [3- (2,6-dichloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with tri-fluoroacetic acid 9- [1- (Biphenyl-2-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methyl-naphthalene-1-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] - undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- (1- [3- (2-chloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -piperidin-4-yl.} - 3-cyclohexylmethyl-l- oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (1,2,3,4-tetrahydro- acridine-9-carbonyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dichloro-4-methanesulfonyl-benzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (quinoline-3-carbonyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (quinoline-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan- 2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (quinoline-6-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-d iaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-morpholin-4-ylbenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-morpholin-4-yl-5-pyrrol-1-yl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (quinoline-8-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan- 2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- (1- (2-methyl-quinoline-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] - undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-4-methyl-6-pyrrolidin-1-yl-benzoyl) -piperidin-4-yl] -3 -cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. {l- [2- (l, l-dioxo-116-thiomorpholin-4-yl) -benzoyl] -piperidin-4-yl.} - l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with acid trifluoroacetic acid 9- [1- (5-Amino-l-phenyl-lH-pyrazole-4-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with trifluoroacetic acid 9-. {1- [5-Amino-l- (4-methoxy-phenyl) -lH-pyrazole-4-carbonyl] -piperidin-4- il.) .5-butyl-3-cyclohexylmethyl-l-oxa3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (l-phenyl-5-trifluo romethyl-L-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { l- [1- (4-methoxy-phenyl) -5-trifluoromethyl-lH-pyrazole-4-carbonyl] -piperidin-4-yl} -1-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; "compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- { 1- [1- (2-methoxy-phenyl) -5-trifluoromethyl-1H-pyrazole-4-carbonyl] -piperidin-4-yl .}. -1. Oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- { 1- [2- (4 -fluoro-benzyl) -5-methyl-2H-pyrazol-3-carbonyl] -piperidin-4-yl.} - l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9-. {l- [1- (4-chloro-phenyl) -5-trifluoromethyl-lH-pyrazole-4-carbonyl] -piperidin-4-yl} -3- cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (lp-tolyl-5-trifluoromethyl- lH-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl- 9-. {L- [l- (4-Fluoro-phenyl) -5- trifluoromethyl-lH-pyrazole-4-carbonyl] -piperidin-4-yl}. -1-oxa-3, 9-diaza- spy [5, 5] undeca n-2-one; compound with trifluoroacetic acid 9- [1- (5-Amino-lp-tolyl-lH-pyrazole-4-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l- oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 9-. { 1- [5-Amino-l- (4-fluoro-phenyl) -lH-pyrazole-4-carbonyl] -piperidin-4-yl} -5-butyl-3-cyclohexylmethyl-l-oxa3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 9-. { 1- [5-Amino-l- (2-methoxy-phenyl) -lH-pyrazole-4-carbonyl] -piperidin-4-yl} -5-butyl-3-cyclohexylmethyl-l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (5-methyl-1-phenyl-1H-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (5-methyl-lp-tolyl-lH-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9-. { l- [l- (4-Chloro-phenyl) -5-methyl-lH-pyrazole-4-carbonyl] -piperidin-4-yl} -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with tri-fluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (5-methyl-2-p-tolyl-2H-pyrazole-3-carbonyl) -piperidin-4-yl] -l-oxa- 3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { l- [2- (4-methoxy-phenyl) -5-methyl-2H-pyrazole-3-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methyl-4,5,6,7-tetrahydro-benzofuran-3-carbonyl) -piperidin-4-? l] -l-oxa -3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3, 5-dimethyl-lH-pyrazole-4-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (2-Bromo-pyridine-3-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-fluoro-pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (3-chloro-pyridine-4-carbonyl) -piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methoxy-pyridine-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methanesulfonylbenzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2 ona; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-trifluoromethoxybenzoyl) -piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5,5] undecan-2 ona; compound with trifluoroacetic acid N-. { 2- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3,9-diaza-spiro [5,5] undec-9-yl) -piperidine-1-carbonyl] -phenyl} -methanesulfonamide; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methyl-5-trifluoromethyl-oxazole-4-carbonyl) -piperidin-4-yl] -l-oxa3, 9-diaza-spiro [ 5, 5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (2-Amino-6-trifluoromethyl-benzoyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-4-nitro-benzoyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro acid [5, 5] undecan-2-one-trifluoroacetic acid, • 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -4-methyl-piperidin-4-yl] -l- oxa-3, 8-diaza-spiro [4, 5] decan-2-one; 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -azetidin-3-yl] -l-oxa-3,8-diaza-spiro [4.5] decan-2- ona; compound with trifluoroacetic acid 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -pyrrolidin-3-yl] -l-oxa-3,8-diaza-spiro [4,5] decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -4- isobutyl-piperidin-4-yl] -l-oxa-3,8-diaza-spiro [4,5] -decan-2-one 4-Butyl-3-cyclohexylmethyl-8- [1- (2,6-dimethyl-benzoyl) -4-ethyl-piperidin-4-yl] -l-oxa-3 , 8-diaza-spiro [4, 5] decan-2-one 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -piperidine -4-yl] -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one; compound with methanesulfonic acid 5-Butyl-3- (4,4-difluoro-cyclohexylmethyl) -9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -l-oxa-3, 9- diazaspiro [5.5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3 , 9-diaza-spiro [5,5] undecan-2-one; compound with 3, 3, 3-trifluoro-propionic acid 5-Butyl-3-cyclohexylmethyl-9- [4-methyl-1- (2,4,5-trimethyl-thiophene-3-carbonyl) -piperidin-4-yl} ] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-dimethylaminobenzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-9- [1- (2-chloro-6-fluoro-benzoyl) -4-methyl-piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3, 9-diaza- spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3, 5-dimethyl-isoxazole-4-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9- diaza-spiro- [5, 5] undecan-2-one; compound, with trifluoroacetic acid 9- [1- (Benzofuran-4-carbonyl) -4-methyl-piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5] , 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-fluoro-6-methoxy-benzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9-diaza- spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3, 5-dimethyl-l-phenyl-lH-pyrazole-4-carbonyl) -4-methyl-piperidin-4-yl] -l- oxa-3, -diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (3, 5-dimethyl-lH-pyrazole-4-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 4-dimethyl-pyridine-3-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9- diaza-spiro- [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [4-methyl-1- (thiophene-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4-methoxy-thiophene-3-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9-diaza- spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (furan-3-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 9- [1- (5-Bromo-furan-3-carbonyl) -4-methyl-piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza- spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methoxy-4,6-dimethyl-pyrimidine-5-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa- 3, 9-diaza-spiro [5, 5] undecan-2-one; compound with tri-fluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-phenyl-pyrimidine-5-carbonyl) -4-methyl-piperidin-4-yl] -l- oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-pyridin-4-yl-pyrimidine-5-carbonyl) -4-methyl-piperidin-4-yl] - l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 3-Cyclohexylmethyl-9- [1- (2,6-dimethyl-benzoyl) -piperidin-4-yl] -5-phenyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 5-dimethyl-furan-3-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [4-methyl-1- (2-methyl-furan-3-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza- spiro [5.5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [5- (4-methoxy-phenyl) -2-methyl-furan-3-carbonyl] -4-methyl-piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [3- (4-methoxy-phenyl) -5-methyl-isoxazole-4-carbonyl] -4-methyl-piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [1- (4-fluoro-phenyl) -3,5-dimethyl-lH-pyrazole-4-carbonyl] -4-methyl-piperidin-4-yl} -1-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid N-. { 3- [4- (5-Butyl-3-cyclohexylmethyl-2-oxo-l-oxa-3, 9-diaza-spiro [5, 5] undec-9-yl) -4-methyl-piperidine-l-carbonyl ] -thofen-2-il} -acetamide; ound with trifluoroacetic acid 5-Butyl-9-. { l- [5- (4-Chloro-phenyl) -2-methyl-furan-3-carbonyl] -4-methyl-piperidin-4-yl} -3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [1- (3,4-dichloro-phenyl) -3,5-dimethyl-lH-pyraz-ol-4-carbonyl] -4-methyl-piperidin-4-yl} -1-oxa-3, 9-diaza-spiro [5, 5] unodecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [1- (3,4-dichloro-phenyl) -3,5-dimethyl-lH-pyrazole-4-carbonyl] -4-methyl-piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; ound with "trifluoroacetic acid 5-Butyl-9- [1- (5-chloro-4-ethyl-thiophene-3-carbonyl) -4-methyl-piperidin-4-yl] -3-cyclohexylmethyl-l-oxa-3 , 9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. {1 - [4, 6-dimethyl-2- (2-methyl- thiazol-4-yl) -pyrimidine-5-carbonyl] -4-methylpiperidin-4-yl.} - l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; ound with acid trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-trifluoromethyl-pyrimidine-5-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9 -diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-methylsulfanyl-pyrimidine-5-carbonyl) - 4-methyl-piperidin-4-yl] -l-oxa-3,9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dichloro-4-methyl-benzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3,9-diaza-spiro- [5,5] undecan-2-one; trifluoric acid 9- [1- (2-Bromo-6-methyl-benzoyl) -4-methyl-piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-l-oxa-3, 9-diaza-spiro [5] , 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dichloro-4-methanesulfonyl-benzoyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5,5] -undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -4-methyl-piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 3-Cyclohexylmethyl-8- [1- (4-methoxy-2,6-dimethyl-benzoyl) -piperidin-4-yl] -4-methyl-l-oxa-3,8-diaza-spiro [ 4, 5] decan-2-one 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9 -diaza-spiro- [5, 5] undecan-2-one; ound with methanesulfonic acid 5-Butyl-9- [1- (4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -3- (tetrahydro-pyran-4-ylmethyl) -l-oxa- 3, 9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,4,6-trimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza- spiro- [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-trifluoromethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5,5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-methylsulfanyl-pyrimidine-5-carbonyl) -piperidin-4- il] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-9- [1- (4,6-dimethyl-2-methylsulfanyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -3- (tetrahydro-pyran-4-ylmethyl) - 1- oxa-3, 9-diaza-espi or [5, 5] undecan-2-one; ound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methanesulfinyl-4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9-. { 1- [4,6-Dimethyl-2- (pyrimidin-2-ylsulfanyl) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9- [1- (2-methanesulfinyl-4,6-dimethyl-pyrimidine-5 acid -carbonyl) -piperidin-4-yl] -9-oxy-l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one-trifluoroacetic; 5-Butyl-3-cyclohexylmethyl-9-. { l- [4,6-Dimethyl-2- (pyridin-2-yloxy) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-phenoxy-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9- diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [4,6-dimethyl-2- (pyridin-2-ylsulfañyl) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5,5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9-. { l- [4,6-Dimethyl-2- (1-methyl-lH-imidazol-2-ylsulfanyl) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one 5-Butyl-3-cyclohexylmethyl-9-. { l- [4,6-Dimethyl-2- (pyridin-4-yloxy) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9-. { 1- [4,6-Dimethyl-2- (2-methyl-imidazol-1-yl) -pyrimidine-5-carbonyl] -piperidin-4-yl} -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-pyridin-4-yl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa- 3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (4,6-dimethyl-2-phenyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- (1- [4,6-dimethyl-2- (2-methyl-thiazol-4-11) -pyrimidine-5-carbonyl] -piperidin-4 -yl.}. -l-oxa-3, 9-diaza-spiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 3 '- [4- (5-butyl-3-cyclohexylmethyl-2- oxo-l-oxa-3, 9-diaza-spiro [5, 5] undec-9-yl) -piperidine-1-carbonyl] -2 ', 4'-dimethyl-biphenyl-4-carboxylic acid compound with trifluoroacetic acid 9- [1- (2-Amino-4,6-dimethyl-pyrimidine-5-carbonyl) -piperidin-4-yl] -5-butyl-3-cyclohexylmethyl-1-oxa-3, 9-diazaspiro [5, 5] -undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2, 4-dimethyl-biphenyl-3-carbonyl) -piperidin-4-yl] -l-oxa -3, 9-diazaspiro [5, 5] undecan-2-one; compound with trifluoroacetic acid 5-Butyl-3-cyclohexylmethyl-9- [1- (2,6-dimethyl-3-pyridin-4-yl-benzoyl ) -piperidin-4-11] -l-oxa-3, 9-diaza-spiro [5,5] -undecan-2-one 4-Butyl-8- [1- (2,6-dimethyl-benzoyl) - piperidin-4-yl] -3- (4-fluo ro-2-trifluoromethyl-benzyl) -l-oxa-3,8-diaza-spiro [4.5] decan-2-one. The compound according to any of claims 1 to 13, characterized in that it is for use as a medicament. 15. The use of one or more compounds according to any of claims 1 to 13 for the manufacture of a medicament for the treatment or prevention of disorders, wherein the modulation of CCR5 receptors is involved. 16. The use according to claim 15, wherein the diseases are infected by the human immunodeficiency virus (HIV), or treatment of AIDS or ARC. 17. A pharmaceutical composition, characterized in that it comprises a therapeutically effective amount of a compound of claim 1 to 13 and at least one pharmaceutically acceptable carrier, diluent or excipient.