IL128668A - Rich in phosphinic acids as inhibitors of metalloproteases - Google Patents

Rich in phosphinic acids as inhibitors of metalloproteases

Info

Publication number: IL128668A
Authority: IL; Israel
Prior art keywords: alkyl; compound; hydroxy; compounds; aryl
Prior art date: 1996-08-28

Application number

IL12866897A

Other languages

English (en)

Hebrew (he)

Other versions

IL128668A0 (en

Original Assignee

Procter & Gamble

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-08-28

Filing date

1997-08-22

Publication date

2002-02-10

1997-08-22 Application filed by Procter & Gamble filed Critical Procter & Gamble

2000-01-31 Publication of IL128668A0 publication Critical patent/IL128668A0/xx

2002-02-10 Publication of IL128668A publication Critical patent/IL128668A/en

Links

239000011159 matrix material Substances 0.000 title description 25
239000003475 metalloproteinase inhibitor Substances 0.000 title description 4
ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 148
-1 heterocycle-alkyl Chemical group 0.000 claims abstract description 60
125000000217 alkyl group Chemical group 0.000 claims abstract description 35
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 19
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 18
125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 15
239000001257 hydrogen Substances 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 11
125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims abstract description 10
150000002148 esters Chemical class 0.000 claims abstract description 10
230000003287 optical effect Effects 0.000 claims abstract description 10
125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 9
125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
125000002947 alkylene group Chemical group 0.000 claims abstract description 7
150000003949 imides Chemical class 0.000 claims abstract description 7
125000006350 alkyl thio alkyl group Chemical group 0.000 claims abstract description 6
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 6
125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 5
125000004474 heteroalkylene group Chemical group 0.000 claims abstract description 5
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims abstract description 3
125000005164 aryl thioalkyl group Chemical group 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 5
125000004945 acylaminoalkyl group Chemical group 0.000 claims abstract 2
125000005041 acyloxyalkyl group Chemical group 0.000 claims abstract 2
125000004946 alkenylalkyl group Chemical group 0.000 claims abstract 2
125000005038 alkynylalkyl group Chemical group 0.000 claims abstract 2
102000005741 Metalloproteases Human genes 0.000 claims description 74
108010006035 Metalloproteases Proteins 0.000 claims description 74
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 56
230000000694 effects Effects 0.000 claims description 37
201000010099 disease Diseases 0.000 claims description 31
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 12
229940080818 propionamide Drugs 0.000 claims description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
238000006467 substitution reaction Methods 0.000 claims description 3
125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
NTLKAXQBFYZMAH-UHFFFAOYSA-N 2-methylpentanamide Chemical compound CCCC(C)C(N)=O NTLKAXQBFYZMAH-UHFFFAOYSA-N 0.000 claims 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 abstract description 11
125000000278 alkyl amino alkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
239000000203 mixture Substances 0.000 description 77
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
238000000034 method Methods 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 43
239000000243 solution Substances 0.000 description 39
238000011282 treatment Methods 0.000 description 31
239000003112 inhibitor Substances 0.000 description 29
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
239000007787 solid Substances 0.000 description 28
238000003756 stirring Methods 0.000 description 27
208000035475 disorder Diseases 0.000 description 25
210000001519 tissue Anatomy 0.000 description 25
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 19
239000003921 oil Substances 0.000 description 19
235000019198 oils Nutrition 0.000 description 19
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
239000003937 drug carrier Substances 0.000 description 18
239000000047 product Substances 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
125000004432 carbon atom Chemical group C* 0.000 description 14
125000000623 heterocyclic group Chemical group 0.000 description 14
238000004809 thin layer chromatography Methods 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
125000003118 aryl group Chemical group 0.000 description 13
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
230000015556 catabolic process Effects 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
102000004190 Enzymes Human genes 0.000 description 11
108090000790 Enzymes Proteins 0.000 description 11
241001465754 Metazoa Species 0.000 description 11
229940088598 enzyme Drugs 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
239000011734 sodium Substances 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 10
239000002552 dosage form Substances 0.000 description 10
239000000126 substance Substances 0.000 description 10
239000003039 volatile agent Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000005842 heteroatom Chemical group 0.000 description 9
206010039073 rheumatoid arthritis Diseases 0.000 description 9
239000002253 acid Substances 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
239000012043 crude product Substances 0.000 description 8
125000005843 halogen group Chemical group 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
150000003254 radicals Chemical class 0.000 description 8
238000002560 therapeutic procedure Methods 0.000 description 8
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000000969 carrier Substances 0.000 description 7
230000003197 catalytic effect Effects 0.000 description 7
239000003086 colorant Substances 0.000 description 7
239000000796 flavoring agent Substances 0.000 description 7
235000013355 food flavoring agent Nutrition 0.000 description 7
125000001072 heteroaryl group Chemical group 0.000 description 7
239000003446 ligand Substances 0.000 description 7
150000004702 methyl esters Chemical class 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
206010028980 Neoplasm Diseases 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
235000001014 amino acid Nutrition 0.000 description 6
150000001413 amino acids Chemical class 0.000 description 6
239000012267 brine Substances 0.000 description 6
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
239000003085 diluting agent Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
201000008482 osteoarthritis Diseases 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
238000007634 remodeling Methods 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000002904 solvent Substances 0.000 description 6
235000019698 starch Nutrition 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
239000003826 tablet Substances 0.000 description 6
230000000699 topical effect Effects 0.000 description 6
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
206010027476 Metastases Diseases 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
102000035195 Peptidases Human genes 0.000 description 5
108091005804 Peptidases Proteins 0.000 description 5
239000004365 Protease Substances 0.000 description 5
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
229930006000 Sucrose Natural products 0.000 description 5
GXJPMBQLUDQIAV-NKWVEPMBSA-N [(4r,5s)-5-ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)O[C@H](CO)[C@H](C=C)O1 GXJPMBQLUDQIAV-NKWVEPMBSA-N 0.000 description 5
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
230000033228 biological regulation Effects 0.000 description 5
239000012230 colorless oil Substances 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
208000015181 infectious disease Diseases 0.000 description 5
239000000314 lubricant Substances 0.000 description 5
230000009401 metastasis Effects 0.000 description 5
HIVDOHPKFIBYPZ-SECBINFHSA-N methyl (2r)-2-(benzylamino)propanoate Chemical compound COC(=O)[C@@H](C)NCC1=CC=CC=C1 HIVDOHPKFIBYPZ-SECBINFHSA-N 0.000 description 5
QVDXUKJJGUSGLS-ZCFIWIBFSA-N methyl (2r)-2-amino-4-methylpentanoate Chemical compound COC(=O)[C@H](N)CC(C)C QVDXUKJJGUSGLS-ZCFIWIBFSA-N 0.000 description 5
DODCBMODXGJOKD-FYZOBXCZSA-N methyl (2r)-2-amino-4-methylpentanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)CC(C)C DODCBMODXGJOKD-FYZOBXCZSA-N 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
230000037390 scarring Effects 0.000 description 5
239000001632 sodium acetate Substances 0.000 description 5
235000017281 sodium acetate Nutrition 0.000 description 5
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000005720 sucrose Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
239000000454 talc Substances 0.000 description 5
235000012222 talc Nutrition 0.000 description 5
229910052623 talc Inorganic materials 0.000 description 5
230000008685 targeting Effects 0.000 description 5
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
102000004127 Cytokines Human genes 0.000 description 4
108090000695 Cytokines Proteins 0.000 description 4
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
101710172711 Structural protein Proteins 0.000 description 4
208000025865 Ulcer Diseases 0.000 description 4
235000010443 alginic acid Nutrition 0.000 description 4
239000000783 alginic acid Substances 0.000 description 4
229920000615 alginic acid Polymers 0.000 description 4
229960001126 alginic acid Drugs 0.000 description 4
150000004781 alginic acids Chemical class 0.000 description 4
230000008901 benefit Effects 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000001768 carboxy methyl cellulose Substances 0.000 description 4
235000010980 cellulose Nutrition 0.000 description 4
229920002678 cellulose Polymers 0.000 description 4
239000001913 cellulose Substances 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
230000006378 damage Effects 0.000 description 4
238000009826 distribution Methods 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
235000003599 food sweetener Nutrition 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000000499 gel Substances 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
150000002431 hydrogen Chemical group 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
208000014674 injury Diseases 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
LITWZVHRFAQHQA-CYBMUJFWSA-N methyl (2r)-2-(benzylamino)-4-methylpentanoate Chemical compound COC(=O)[C@@H](CC(C)C)NCC1=CC=CC=C1 LITWZVHRFAQHQA-CYBMUJFWSA-N 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
238000007911 parenteral administration Methods 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
230000002265 prevention Effects 0.000 description 4
239000000600 sorbitol Substances 0.000 description 4
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125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
241000416162 Astragalus gummifer Species 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
239000001856 Ethyl cellulose Substances 0.000 description 3
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108010026132 Gelatinases Proteins 0.000 description 3
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
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GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
229920001615 Tragacanth Polymers 0.000 description 3
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BHYBJNSQCWMPAJ-UHFFFAOYSA-N [ethoxy(ethyl)phosphoryl]benzene Chemical compound CCOP(=O)(CC)C1=CC=CC=C1 BHYBJNSQCWMPAJ-UHFFFAOYSA-N 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
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MBRRYUQWSOODEO-GFCCVEGCSA-N benzyl (2r)-2-amino-4-methylpentanoate Chemical compound CC(C)C[C@@H](N)C(=O)OCC1=CC=CC=C1 MBRRYUQWSOODEO-GFCCVEGCSA-N 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
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238000003018 immunoassay Methods 0.000 description 3
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QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
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235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
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Classifications

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- C07—ORGANIC CHEMISTRY
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Physical Education & Sports Medicine (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Immunology (AREA)
Cardiology (AREA)
Biomedical Technology (AREA)
Dermatology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

IL12866897A 1996-08-28 1997-08-22 Rich in phosphinic acids as inhibitors of metalloproteases IL128668A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2476596P	1996-08-28	1996-08-28
PCT/US1997/014556 WO1998008853A1 (en)	1996-08-28	1997-08-22	Phosphinic acid amides as matrix metalloprotease inhibitors

Publications (2)

Publication Number	Publication Date
IL128668A0 IL128668A0 (en)	2000-01-31
IL128668A true IL128668A (en)	2002-02-10

Family

ID=21822291

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12866897A IL128668A (en)	1996-08-28	1997-08-22	Rich in phosphinic acids as inhibitors of metalloproteases

Country Status (27)

Country	Link
US (1)	US5830915A (de)
EP (1)	EP0925303B1 (de)
JP (1)	JP3539736B2 (de)
KR (1)	KR20000035925A (de)
CN (1)	CN1228780A (de)
AR (1)	AR009357A1 (de)
AT (1)	ATE226590T1 (de)
AU (1)	AU732653B2 (de)
BR (1)	BR9713182A (de)
CA (1)	CA2264254C (de)
CO (1)	CO4900033A1 (de)
CZ (1)	CZ63699A3 (de)
DE (1)	DE69716619T2 (de)
DK (1)	DK0925303T3 (de)
HU (1)	HUP9903916A3 (de)
ID (1)	ID18145A (de)
IL (1)	IL128668A (de)
NO (1)	NO990857L (de)
NZ (1)	NZ334258A (de)
PE (1)	PE107698A1 (de)
PL (1)	PL331854A1 (de)
RU (1)	RU2170232C2 (de)
SK (1)	SK25499A3 (de)
TR (1)	TR199900399T2 (de)
TW (1)	TW518338B (de)
WO (1)	WO1998008853A1 (de)
ZA (1)	ZA977700B (de)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030206874A1 (en) *	1996-11-21	2003-11-06	The Proctor & Gamble Company	Promoting whole body health
JP2001513484A (ja)	1997-07-31	2001-09-04	ザプロクターアンドギャンブルカンパニー	非環式メタロプロテアーゼ阻害剤
US6846478B1 (en)	1998-02-27	2005-01-25	The Procter & Gamble Company	Promoting whole body health
DE19850072A1 (de) *	1998-10-30	2000-05-04	Bayer Ag	Phosphinat-Peptidanaloga zur Behandlung von fibrotischen Erkrankungen
US6277885B1 (en)	1999-01-27	2001-08-21	American Cyanamid Company	Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
US6313123B1 (en)	1999-01-27	2001-11-06	American Cyanamid Company	Acetylenic sulfonamide thiol tace inhibitors
US6225311B1 (en)	1999-01-27	2001-05-01	American Cyanamid Company	Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors
AR035313A1 (es) *	1999-01-27	2004-05-12	Wyeth Corp	Inhibidores de tace acetilenicos de acido hidroxamico de sulfonamida a base de alfa-aminoacidos, composiciones farmaceuticas y el uso de los mismos para la manufactura de medicamentos.
US6753337B2 (en)	1999-01-27	2004-06-22	Wyeth Holdings Corporation	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors
US6340691B1 (en)	1999-01-27	2002-01-22	American Cyanamid Company	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors
US6200996B1 (en)	1999-01-27	2001-03-13	American Cyanamid Company	Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors
BR0007784A (pt)	1999-01-27	2002-02-05	American Cyanamid Co	Composto, método para inibir mudanças patológicas mediadas pela enzima que converte o tnf-alfa (tace) em um mamìfero, composição farmacêutica, e, processo para preparar um composto
US6762178B2 (en)	1999-01-27	2004-07-13	Wyeth Holdings Corporation	Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
US6326516B1 (en)	1999-01-27	2001-12-04	American Cyanamid Company	Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors
US6946473B2 (en)	1999-01-27	2005-09-20	Wyeth Holdings Corporation	Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors
CZ20012710A3 (cs) *	1999-01-27	2002-04-17	American Cyanamid Company	Acetylenické arylové sulfonamidohydroxamové a fosfinamidohydroxamové kyseliny jako inhibitory TACE
US6197770B1 (en)	1999-03-03	2001-03-06	The Procter & Gamble Co.	Alkenyl- and alkynl-containing metalloprotease inhibitors
US6297337B1 (en)	1999-05-19	2001-10-02	Pmd Holdings Corp.	Bioadhesive polymer compositions
US6312474B1 (en)	1999-09-15	2001-11-06	Bio-Vascular, Inc.	Resorbable implant materials
US8283135B2 (en) *	2000-06-30	2012-10-09	The Procter & Gamble Company	Oral care compositions containing combinations of anti-bacterial and host-response modulating agents
CN1536989A (zh) *	2000-06-30	2004-10-13		促进全身健康
JP2004517038A (ja) *	2000-06-30	2004-06-10	ザ、プロクター、エンド、ギャンブル、カンパニー	全身の健康増進
KR20030018053A (ko) *	2000-07-18	2003-03-04	레오 파마 에이/에스	매트릭스 메탈로프로티나제 억제제
FR2814950B1 (fr) *	2000-10-05	2003-08-08	Oreal	Utilisation d'au moins un extrait d'au moins un vegetal de la famille des ericaceae, dans des compositions destinees a traiter les signes cutanes du vieillissement
US6693099B2 (en) *	2000-10-17	2004-02-17	The Procter & Gamble Company	Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance
US6376514B1 (en)	2000-10-17	2002-04-23	The Procter & Gamble Co.	Substituted six-membered heterocyclic compounds useful for treating multidrug resistance and compositions and methods thereof
EP1440057A1 (de)	2001-11-01	2004-07-28	Wyeth Holdings Corporation	Allenische arylsulfonamidhydroxamsäure als matrix-metalloproteinase und tace inhibitoren
PE20030701A1 (es)	2001-12-20	2003-08-21	Schering Corp	Compuestos para el tratamiento de trastornos inflamatorios
CN1714096A (zh)	2002-01-18	2005-12-28	利奥制药有限公司	Mmp抑制剂
US7199155B2 (en)	2002-12-23	2007-04-03	Wyeth Holdings Corporation	Acetylenic aryl sulfonate hydroxamic acid TACE and matrix metalloproteinase inhibitors
AU2003300076C1 (en)	2002-12-30	2010-03-04	Angiotech International Ag	Drug delivery from rapid gelling polymer composition
US7144588B2 (en)	2003-01-17	2006-12-05	Synovis Life Technologies, Inc.	Method of preventing surgical adhesions
EP1449538A1 (de) *	2003-02-21	2004-08-25	Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.	Modulation der EGF Rezeptor Signalübertragung durch Hemmung von TACE oder Amphiregulin
EP2128167A4 (de) *	2007-03-09	2012-01-04	Univ Nagoya Nat Univ Corp	Phosphoramidverbindung, verfahren zu deren herstellung, ligand, komplex, katalysator und verfahren zur herstellung eines optisch aktiven alkohols
TW201141536A (en)	2009-12-21	2011-12-01	Colgate Palmolive Co	Oral care compositions and methods
JP6002764B2 (ja) *	2011-06-29	2016-10-05	ヤンセンファーマシューティカエヌ．ベー．	マトリックスメタロプロテアーゼのアロステリックなプロセシング阻害因子を使用する処置方法
RU2488587C1 (ru) *	2012-05-23	2013-07-27	Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Казанский национальный исследовательский технологический университет"	Анилид гидроксиметиланилинометилфосфиновой кислоты (амидофос) в качестве биостимулятора активного ила в процессе очистки сточных вод и способ его получения
ES2941969T3 (es)	2015-10-23	2023-05-29	Navitor Pharm Inc	Moduladores de la interacción de Sestrina-GATOR2 y sus usos
WO2017117130A1 (en)	2015-12-28	2017-07-06	The United States Of America, As Represented By The Secretary, Department Of Health & Human Services	Methods for inhibiting human immunodeficiency virus (hiv) release from infected cells
CN107709288A (zh) *	2016-02-03	2018-02-16	四川海思科制药有限公司	一种磷酰胺衍生物及制备方法和用途
JP7542935B2 (ja) *	2016-04-29	2024-09-02	オフィレックスインコーポレイテッド	溶血、脳浮腫および急性腎障害を引き起こす病態の治療のためのｐｌａ２およびｈｍｇ－ｃｏａ阻害剤
CN106905183B (zh) *	2017-02-24	2018-07-31	三峡大学	一类含氨基的ɑ-酰氧基羰基酰胺类衍生物，制备方法及其应用
CN110809467B (zh)	2017-04-26	2023-03-10	纳维托制药有限公司	Sestrin-gator2相互作用的调节剂及其用途
MX2021004710A (es)	2018-10-24	2021-06-04	Navitor Pharm Inc	Compuestos polimorficos y usos de los mismos.
BR112022008287A2 (pt)	2019-11-01	2022-07-26	Navitor Pharm Inc	Métodos de tratamento usando um modulador de mtorc1

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8601368D0 (en) *	1986-01-21	1986-02-26	Ici America Inc	Hydroxamic acids
DK77487A (da) *	1986-03-11	1987-09-12	Hoffmann La Roche	Hydroxylaminderivater
FR2609289B1 (fr) *	1987-01-06	1991-03-29	Bellon Labor Sa Roger	Nouveaux composes a activite d'inhibiteurs de collagenase, procede pour les preparer et compositions pharmaceutiques contenant ces composes
GB8827305D0 (en) *	1988-11-23	1988-12-29	British Bio Technology	Compounds
GB8919251D0 (en) *	1989-08-24	1989-10-04	British Bio Technology	Compounds
DE4011172A1 (de) *	1990-04-06	1991-10-10	Degussa	Verbindungen zur bekaempfung von pflanzenkrankheiten
US5189178A (en) *	1990-11-21	1993-02-23	Galardy Richard E	Matrix metalloprotease inhibitors
US5183900A (en) *	1990-11-21	1993-02-02	Galardy Richard E	Matrix metalloprotease inhibitors
GB9102635D0 (en) *	1991-02-07	1991-03-27	British Bio Technology	Compounds
GB9107368D0 (en) *	1991-04-08	1991-05-22	Smithkline Beecham Plc	Novel compounds
IL98681A (en) *	1991-06-30	1997-06-10	Yeda Rehovot And Dev Company L	Pharmaceutical compositions comprising hydroxamate derivatives for iron removal from mammalian cells and from pathogenic organisms and some novel hydroxamate derivatives
DE4127842A1 (de) *	1991-08-22	1993-02-25	Rhone Poulenc Rorer Gmbh	5-((omega)-arylalky)-2-thienyl alkansaeuren, ihre salze und/oder ihre derivate
JPH05125029A (ja) *	1991-11-06	1993-05-21	Yamanouchi Pharmaceut Co Ltd	新規なアミド化合物又はその塩
WO1993020047A1 (en) *	1992-04-07	1993-10-14	British Bio-Technology Limited	Hydroxamic acid based collagenase and cytokine inhibitors
EP1002556A3 (de) *	1992-05-01	2001-01-10	British Biotech Pharmaceuticals Limited	Verwendung von MMP Hemmer
AU666727B2 (en) *	1992-06-25	1996-02-22	F. Hoffmann-La Roche Ag	Hydroxamic acid derivatives
GB9215665D0 (en) *	1992-07-23	1992-09-09	British Bio Technology	Compounds
GB9223904D0 (en) *	1992-11-13	1993-01-06	British Bio Technology	Inhibition of cytokine production
US5455258A (en) *	1993-01-06	1995-10-03	Ciba-Geigy Corporation	Arylsulfonamido-substituted hydroxamic acids
US5514716A (en) *	1994-02-25	1996-05-07	Sterling Winthrop, Inc.	Hydroxamic acid and carboxylic acid derivatives, process for their preparation and use thereof
CN1151157A (zh) *	1994-06-22	1997-06-04	英国生物技术药物有限公司	金属蛋白酶抑制剂

1997
- 1997-08-22 KR KR1019997001661A patent/KR20000035925A/ko active IP Right Grant
- 1997-08-22 AU AU41531/97A patent/AU732653B2/en not_active Ceased
- 1997-08-22 JP JP51171698A patent/JP3539736B2/ja not_active Expired - Fee Related
- 1997-08-22 NZ NZ334258A patent/NZ334258A/xx unknown
- 1997-08-22 CN CN97197546A patent/CN1228780A/zh active Pending
- 1997-08-22 CZ CZ99636A patent/CZ63699A3/cs unknown
- 1997-08-22 TR TR1999/00399T patent/TR199900399T2/xx unknown
- 1997-08-22 DK DK97939444T patent/DK0925303T3/da active
- 1997-08-22 AT AT97939444T patent/ATE226590T1/de not_active IP Right Cessation
- 1997-08-22 RU RU99106245/04A patent/RU2170232C2/ru active
- 1997-08-22 IL IL12866897A patent/IL128668A/en not_active IP Right Cessation
- 1997-08-22 HU HU9903916A patent/HUP9903916A3/hu unknown
- 1997-08-22 BR BR9713182-2A patent/BR9713182A/pt unknown
- 1997-08-22 EP EP97939444A patent/EP0925303B1/de not_active Expired - Lifetime
- 1997-08-22 DE DE69716619T patent/DE69716619T2/de not_active Expired - Fee Related
- 1997-08-22 WO PCT/US1997/014556 patent/WO1998008853A1/en not_active Application Discontinuation
- 1997-08-22 PL PL97331854A patent/PL331854A1/xx unknown
- 1997-08-22 SK SK254-99A patent/SK25499A3/sk unknown
- 1997-08-22 CA CA002264254A patent/CA2264254C/en not_active Expired - Fee Related
- 1997-08-26 US US08/918,950 patent/US5830915A/en not_active Expired - Fee Related
- 1997-08-27 AR ARP970103898A patent/AR009357A1/es unknown
- 1997-08-27 ZA ZA9707700A patent/ZA977700B/xx unknown
- 1997-08-27 CO CO97049512A patent/CO4900033A1/es unknown
- 1997-08-28 ID IDP972999A patent/ID18145A/id unknown
- 1997-08-28 PE PE1997000765A patent/PE107698A1/es not_active Application Discontinuation
1998
- 1998-02-03 TW TW087101222A patent/TW518338B/zh active
1999
- 1999-02-23 NO NO990857A patent/NO990857L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
PL331854A1 (en)	1999-08-16
WO1998008853A1 (en)	1998-03-05
JP2000515167A (ja)	2000-11-14
US5830915A (en)	1998-11-03
ID18145A (id)	1998-03-05
HUP9903916A3 (en)	2001-06-28
RU2170232C2 (ru)	2001-07-10
NZ334258A (en)	2000-11-24
KR20000035925A (ko)	2000-06-26
AU732653B2 (en)	2001-04-26
CO4900033A1 (es)	2000-03-27
CZ63699A3 (cs)	1999-07-14
EP0925303A1 (de)	1999-06-30
CA2264254A1 (en)	1998-03-05
HUP9903916A2 (hu)	2001-05-28
ZA977700B (en)	1998-02-23
NO990857D0 (no)	1999-02-23
JP3539736B2 (ja)	2004-07-07
DK0925303T3 (da)	2003-02-24
AU4153197A (en)	1998-03-19
IL128668A0 (en)	2000-01-31
SK25499A3 (en)	2000-03-13
TR199900399T2 (xx)	1999-06-21
ATE226590T1 (de)	2002-11-15
PE107698A1 (es)	1999-02-11
EP0925303B1 (de)	2002-10-23
DE69716619T2 (de)	2003-06-26
TW518338B (en)	2003-01-21
DE69716619D1 (en)	2002-11-28
NO990857L (no)	1999-04-28
AR009357A1 (es)	2000-04-12
CA2264254C (en)	2003-03-11
BR9713182A (pt)	1999-11-03
CN1228780A (zh)	1999-09-15

Legal Events

Date	Code	Title
2002-06-30	FF	Patent granted
2002-08-14	KB	Patent renewed
2003-10-31	KB	Patent renewed
2008-06-05	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0925303B1 (de)	2002-10-23	Phosphinsäureamide als matrix metalloprotease inhibitoren
WO1998008853A9 (en)	1998-08-06	Phosphinic acid amides as matrix metalloprotease inhibitors
EP0923561B1 (de)	2002-10-23	Heterozyklische metalloproteaseinhibitoren
US6218389B1 (en)	2001-04-17	Acyclic metalloprotease inhibitors
EP0927168B1 (de)	2002-11-06	1,3-diheterozyklische metalloprotease inhibitoren
AU731319B2 (en)	2001-03-29	Heterocyclic metalloprotease inhibitors
US6121272A (en)	2000-09-19	Bidentate metalloprotease inhibitors
IL128667A (en)	2002-04-21	Spirocyclic metroprotease inhibitors and pharmaceutical preparations containing them
MXPA99002064A (en)	1999-09-20	Heterocyclic metalloprotease inhibitors
MXPA99002067A (en)	1999-09-20	Heterocyclic metalloprotease inhibitors
MXPA00001147A (en)	2001-12-04	Acyclic metalloprotease inhibitors