AU2001239331A1 - Derivatives of quinoline as alpha-2 antagonists - Google Patents

Derivatives of quinoline as alpha-2 antagonists

Info

Publication number: AU2001239331A1
Authority: AU; Australia
Prior art keywords: alkyl; phenyl; compound; alkoxy; mono
Prior art date: 2000-03-01
Legal status (The legal status 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 status listed.): Abandoned

Application number

AU2001239331A

Other languages

English (en)

Inventor

Mia Engstrom

Antti Haapalinna

Anna-Marja Hoffren

Iisa Hoglund

Jukka Sallinen

Harri Salo

Juha-Matti Savola

Andrei Tauber

Siegfried Wurster

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Orion Oyj

Juvanita Pharma Ltd Oy

Original Assignee

Orion Oyj

Juvanita Pharma Ltd Oy

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.)

2000-03-01

Filing date

2001-02-28

Publication date

2001-09-12

2001-02-28 Application filed by Orion Oyj, Juvanita Pharma Ltd Oy filed Critical Orion Oyj

2001-09-12 Publication of AU2001239331A1 publication Critical patent/AU2001239331A1/en

Status Abandoned legal-status Critical Current

Links

239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 title description 12
125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
125000000217 alkyl group Chemical group 0.000 claims description 200
150000001875 compounds Chemical class 0.000 claims description 136
125000003545 alkoxy group Chemical group 0.000 claims description 72
229910052736 halogen Inorganic materials 0.000 claims description 66
150000002367 halogens Chemical class 0.000 claims description 66
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
125000003282 alkyl amino group Chemical group 0.000 claims description 47
125000001424 substituent group Chemical group 0.000 claims description 42
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
125000003342 alkenyl group Chemical group 0.000 claims description 32
-1 1- imidazolyl Chemical group 0.000 claims description 30
125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
150000002148 esters Chemical class 0.000 claims description 20
239000005557 antagonist Substances 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
125000002837 carbocyclic group Chemical group 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
210000003169 central nervous system Anatomy 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 10
125000001624 naphthyl group Chemical group 0.000 claims description 10
108060003345 Adrenergic Receptor Proteins 0.000 claims description 9
102000017910 Adrenergic receptor Human genes 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 7
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 7
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 5
YEGLCEJPSSYEQE-UHFFFAOYSA-N 3-ethyl-2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 YEGLCEJPSSYEQE-UHFFFAOYSA-N 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
QYNDZEYXHRVXBK-UHFFFAOYSA-N 2,7-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C=12CC(C)CCC2=NC2=CC=C(C)C=C2C=1NC(C=C1)=CC=C1N1CCN(C)CC1 QYNDZEYXHRVXBK-UHFFFAOYSA-N 0.000 claims description 3
GZPDMTWJWCKXNJ-UHFFFAOYSA-N 2-[4-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)phenyl]piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=CC=CC=C12 GZPDMTWJWCKXNJ-UHFFFAOYSA-N 0.000 claims description 3
VBDVCLHMPVSOQZ-UHFFFAOYSA-N 2-[4-[4-(acridin-9-ylamino)phenyl]piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 VBDVCLHMPVSOQZ-UHFFFAOYSA-N 0.000 claims description 3
VHXSDKWBFNFFHS-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C=12CC(C)CCC2=NC2=CC=CC=C2C=1NC(C=C1)=CC=C1N1CCN(C)CC1 VHXSDKWBFNFFHS-UHFFFAOYSA-N 0.000 claims description 3
MKIZKMFJTXEUHC-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=CC(C)=NC2=CC=CC=C12 MKIZKMFJTXEUHC-UHFFFAOYSA-N 0.000 claims description 3
NAUGYWORANWRRP-UHFFFAOYSA-N 3-ethyl-6-methoxy-2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC(OC)=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 NAUGYWORANWRRP-UHFFFAOYSA-N 0.000 claims description 3
WWLIQWZZBMOLAS-UHFFFAOYSA-N 8-fluoro-n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=CC=CC(F)=C12 WWLIQWZZBMOLAS-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
YTMDIHJFKUKUBO-UHFFFAOYSA-N n-(2,5-diethoxy-4-morpholin-4-ylphenyl)acridin-9-amine Chemical compound CCOC=1C=C(NC=2C3=CC=CC=C3N=C3C=CC=CC3=2)C(OCC)=CC=1N1CCOCC1 YTMDIHJFKUKUBO-UHFFFAOYSA-N 0.000 claims description 3
ZHMTVZXBRVBKJJ-UHFFFAOYSA-N n-[4-(4-cyclopropylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C1CC1N1CCN(C=2C=CC(NC=3C4=CC=CC=C4N=C4C=CC=CC4=3)=CC=2)CC1 ZHMTVZXBRVBKJJ-UHFFFAOYSA-N 0.000 claims description 3
CPXJYPKLTDRTNF-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4,5,6,7,8-octahydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=C1CCCC2 CPXJYPKLTDRTNF-UHFFFAOYSA-N 0.000 claims description 3
ASJSNRRPCZXGRL-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=CC=CC=C12 ASJSNRRPCZXGRL-UHFFFAOYSA-N 0.000 claims description 3
LVWWUTHVDJHKIR-UHFFFAOYSA-N n-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 LVWWUTHVDJHKIR-UHFFFAOYSA-N 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
YAPCYKZPQAMZQI-UHFFFAOYSA-N 2,3-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(C)C(C)=NC2=CC=CC=C12 YAPCYKZPQAMZQI-UHFFFAOYSA-N 0.000 claims description 2
CEAASZYIQFCQJH-UHFFFAOYSA-N 3-ethyl-2,6-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC(C)=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 CEAASZYIQFCQJH-UHFFFAOYSA-N 0.000 claims description 2
GZBPAEYFMVRUNB-UHFFFAOYSA-N 3-ethyl-2,8-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C(C)=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 GZBPAEYFMVRUNB-UHFFFAOYSA-N 0.000 claims description 2
MAUXHXJBQAWVSI-UHFFFAOYSA-N 3-ethyl-n,2-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC=CC2=C1N(C)C(C=C1)=CC=C1N1CCN(C)CC1 MAUXHXJBQAWVSI-UHFFFAOYSA-N 0.000 claims description 2
YZUCBZHBBMZNFL-UHFFFAOYSA-N 4-(3-chloro-4-imidazol-1-ylanilino)-7-methoxy-6-nitroquinoline-3-carbonitrile Chemical compound C=12C=C([N+]([O-])=O)C(OC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1N1C=CN=C1 YZUCBZHBBMZNFL-UHFFFAOYSA-N 0.000 claims description 2
BXVCYRBPPBQKEN-UHFFFAOYSA-N 4-[4-(4-methylpiperazin-1-yl)anilino]quinoline-3-carbonitrile Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(C#N)C=NC2=CC=CC=C12 BXVCYRBPPBQKEN-UHFFFAOYSA-N 0.000 claims description 2
DUYKGBPLYMVLEY-UHFFFAOYSA-N 4-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]phenyl]-n,n-diethylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)N(CC)CC)CCN1C(C=C1)=CC=C1NC1=C(C=CC(Cl)=C2)C2=NC2=CC=C(OC)C=C12 DUYKGBPLYMVLEY-UHFFFAOYSA-N 0.000 claims description 2
QSUPSFCOOLCORC-UHFFFAOYSA-N 4-methoxy-n-[4-(4-methylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C12=CC=CC=C2N=C2C(OC)=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 QSUPSFCOOLCORC-UHFFFAOYSA-N 0.000 claims description 2
GOVQEKRSQZBPAX-UHFFFAOYSA-N [1-[4-(acridin-9-ylamino)phenyl]piperidin-3-yl]methanol Chemical compound C1C(CO)CCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 GOVQEKRSQZBPAX-UHFFFAOYSA-N 0.000 claims description 2
150000001555 benzenes Chemical group 0.000 claims description 2
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
KJQWJHXJHKKTTD-UHFFFAOYSA-N n-[4-(4-benzylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C1CN(C=2C=CC(NC=3C4=CC=CC=C4N=C4C=CC=CC4=3)=CC=2)CCN1CC1=CC=CC=C1 KJQWJHXJHKKTTD-UHFFFAOYSA-N 0.000 claims description 2
LDFIRHZOIKFLQJ-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-7,8,9,10-tetrahydro-6h-cyclohepta[b]quinolin-11-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCCC2)C2=NC2=CC=CC=C12 LDFIRHZOIKFLQJ-UHFFFAOYSA-N 0.000 claims description 2
SKJFMEQTIWVLCD-UHFFFAOYSA-N n-[4-(4-methylpiperidin-1-yl)phenyl]acridin-9-amine Chemical compound C1CC(C)CCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 SKJFMEQTIWVLCD-UHFFFAOYSA-N 0.000 claims description 2
SSSIZHIHVRNNHH-UHFFFAOYSA-N n-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C=12C=CC=CC2=NC2=CC=CC=C2C=1N(C)C(C=C1)=CC=C1N1CCN(C)CC1 SSSIZHIHVRNNHH-UHFFFAOYSA-N 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 15
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
FXCDZMFOKWHQFP-UHFFFAOYSA-N 1,1,3,3-tetramethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-2,4-dihydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C2C(C)(C)CC(C)(C)CC2=NC2=CC=CC=C12 FXCDZMFOKWHQFP-UHFFFAOYSA-N 0.000 claims 1
XMXAKWQIZRUKOE-UHFFFAOYSA-N 4-[4-[(7-chloro-2-methylquinolin-4-yl)amino]phenyl]-n,n-diethylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)N(CC)CC)CCN1C(C=C1)=CC=C1NC1=CC(C)=NC2=CC(Cl)=CC=C12 XMXAKWQIZRUKOE-UHFFFAOYSA-N 0.000 claims 1
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
NOJDKJGJUVAORM-UHFFFAOYSA-N n-(4-pyrrolidin-1-ylphenyl)acridin-9-amine Chemical compound C1CCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 NOJDKJGJUVAORM-UHFFFAOYSA-N 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
238000000034 method Methods 0.000 description 50
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
125000004356 hydroxy functional group Chemical group O* 0.000 description 26
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
238000005160 1H NMR spectroscopy Methods 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
HSWPZIDYAHLZDD-UHFFFAOYSA-N atipamezole Chemical compound C1C2=CC=CC=C2CC1(CC)C1=CN=CN1 HSWPZIDYAHLZDD-UHFFFAOYSA-N 0.000 description 17
229960003002 atipamezole Drugs 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
230000000694 effects Effects 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 15
229940125904 compound 1 Drugs 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
KGIGZIBMXZQUSF-UHFFFAOYSA-N n-(4-piperazin-1-ylphenyl)acridin-9-amine Chemical compound C1CNCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 KGIGZIBMXZQUSF-UHFFFAOYSA-N 0.000 description 12
MOZNZNKHRXRLLF-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1 MOZNZNKHRXRLLF-UHFFFAOYSA-N 0.000 description 10
BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
238000012360 testing method Methods 0.000 description 9
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 8
241001465754 Metazoa Species 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
238000002474 experimental method Methods 0.000 description 8
239000000243 solution Substances 0.000 description 8
VWOJSRICSKDKAW-UHFFFAOYSA-N 1-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCNCC1 VWOJSRICSKDKAW-UHFFFAOYSA-N 0.000 description 7
FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 description 7
230000008485 antagonism Effects 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
150000003254 radicals Chemical class 0.000 description 7
VGVHNLRUAMRIEW-UHFFFAOYSA-N 4-methylcyclohexan-1-one Chemical compound CC1CCC(=O)CC1 VGVHNLRUAMRIEW-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 6
HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 description 6
229960004253 dexmedetomidine Drugs 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
239000000203 mixture Substances 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
241000282414 Homo sapiens Species 0.000 description 5
239000000556 agonist Substances 0.000 description 5
230000027455 binding Effects 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
238000003756 stirring Methods 0.000 description 5
GZNDUKANJZIZOT-UHFFFAOYSA-N 1-methyl-4-(4-nitrophenyl)piperazine Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C=C1 GZNDUKANJZIZOT-UHFFFAOYSA-N 0.000 description 4
102000012305 Alpha 2A adrenoceptor Human genes 0.000 description 4
108050002822 Alpha 2A adrenoceptor Proteins 0.000 description 4
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 4
102000015006 alpha2-adrenergic receptor activity proteins Human genes 0.000 description 4
238000001816 cooling Methods 0.000 description 4
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
239000003480 eluent Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
230000009182 swimming Effects 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
RGHQKFQZGLKBCF-UHFFFAOYSA-N 2-bromoethyl acetate Chemical compound CC(=O)OCCBr RGHQKFQZGLKBCF-UHFFFAOYSA-N 0.000 description 3
OQJMHUOCLRCSED-UHFFFAOYSA-N 3,3,5,5-tetramethylcyclohexan-1-one Chemical compound CC1(C)CC(=O)CC(C)(C)C1 OQJMHUOCLRCSED-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
102000012563 Alpha 2C adrenoceptor Human genes 0.000 description 3
108050002082 Alpha 2C adrenoceptor Proteins 0.000 description 3
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AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
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IHBKDAUSAHOUAN-UHFFFAOYSA-N n-(4-morpholin-4-ylphenyl)acridin-9-amine Chemical compound C1COCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 IHBKDAUSAHOUAN-UHFFFAOYSA-N 0.000 description 1
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RXXDJBWYJTWSKV-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=CC=NC2=CC=CC=C12 RXXDJBWYJTWSKV-UHFFFAOYSA-N 0.000 description 1
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230000009871 nonspecific binding Effects 0.000 description 1
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SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
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150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
230000006461 physiological response Effects 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical group OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
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238000010149 post-hoc-test Methods 0.000 description 1
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230000003389 potentiating effect Effects 0.000 description 1
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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208000020016 psychiatric disease Diseases 0.000 description 1
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QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical compound C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 description 1
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URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
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150000003892 tartrate salts Chemical class 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
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239000011534 wash buffer Substances 0.000 description 1
BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
229960000317 yohimbine Drugs 0.000 description 1
AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1

Classifications

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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
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- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- A—HUMAN NECESSITIES
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/08—Nitrogen atoms
- C07D219/10—Nitrogen atoms attached in position 9
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Psychiatry (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Obesity (AREA)
Endocrinology (AREA)
Hematology (AREA)
Emergency Medicine (AREA)
Psychology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Gynecology & Obstetrics (AREA)
Reproductive Health (AREA)
Child & Adolescent Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Quinoline Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

AU2001239331A 2000-03-01 2001-02-28 Derivatives of quinoline as alpha-2 antagonists Abandoned AU2001239331A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FI20000480		2000-03-01
FI20000480A FI20000480A0 (fi)	2000-03-01	2000-03-01	Kinoliini- ja naftaleenijohdannaisia alfa-2 antagonisteina
PCT/FI2001/000203 WO2001064645A2 (en)	2000-03-01	2001-02-28	Derivatives of quinoline as alpha-2 antagonists

Publications (1)

Publication Number	Publication Date
AU2001239331A1 true AU2001239331A1 (en)	2001-09-12

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AU2001239331A Abandoned AU2001239331A1 (en)	2000-03-01	2001-02-28	Derivatives of quinoline as alpha-2 antagonists

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EP (1)	EP1263733A2 (et)
JP (1)	JP2003525274A (et)
KR (1)	KR20020089372A (et)
CN (1)	CN1468224A (et)
AR (1)	AR034249A1 (et)
AU (1)	AU2001239331A1 (et)
BR (1)	BR0108816A (et)
CA (1)	CA2400657A1 (et)
CZ (1)	CZ20022880A3 (et)
EE (1)	EE200200490A (et)
FI (1)	FI20000480A0 (et)
HU (1)	HUP0204458A3 (et)
IL (1)	IL151093A0 (et)
MX (1)	MXPA02008402A (et)
NO (1)	NO20024159D0 (et)
PE (1)	PE20011084A1 (et)
PL (1)	PL357874A1 (et)
RU (1)	RU2002125944A (et)
SK (1)	SK12332002A3 (et)
WO (1)	WO2001064645A2 (et)
ZA (1)	ZA200206956B (et)

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WO2004067513A1 (en) *	2003-01-27	2004-08-12	Oy Juvantia Pharma Ltd	Antagonists for alpha-2 adrenoceptors
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WO2007078335A2 (en) *	2005-12-21	2007-07-12	Decode Genetics, Ehf.	Biaryl nitrogen heterocycle inhibitors of lta4h for treating inflammation
JP2009537602A (ja) *	2006-05-22	2009-10-29	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	薬剤として用いるための置換ピラジノン誘導体
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EP2014656A3 (en)	2007-06-11	2011-08-24	High Point Pharmaceuticals, LLC	New heteocyclic h3 antagonists
TWI457122B (zh)	2007-07-20	2014-10-21	Orion Corp	作為用於治療周邊和中央神經系統疾病之alpha2C拮抗劑的2,3－二氫苯並[1,4]戴奧辛－2－基甲基衍生物
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CN103524413B (zh) *	2012-07-04	2016-04-20	江苏先声药物研究有限公司	氢化吖啶衍生物及其应用
JOP20200052A1 (ar) *	2013-12-19	2017-06-16	Bayer Pharma AG	بيبريدينيل تتراهيدرو كوينولينات مستبدلة واستخدامها كمعضدات مستقبل أدريني ألفا- 2c
JP6483804B2 (ja)	2014-03-31	2019-03-13	ミレクスファーマシューティカルズ，エルエルシーＭｉｒｘＰｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｌｌｃ	新規なｈｄｍｘ阻害剤およびガン治療のためのその使用
WO2016135140A1 (en)	2015-02-23	2016-09-01	Cemm - Forschungszentrum Für Molekulare Medizin Gmbh	4-aminoquinazoline derivatives as mth1 inhibitors for the therapy of cancer
WO2016135137A1 (en)	2015-02-23	2016-09-01	Cemm - Forschungszentrum Für Molekulare Medizin Gmbh	Substituted 4-(phenylamino)quinoline derivatives as mth1 inhibitors for the therapy of cancer
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GB9510757D0 (en) *	1994-09-19	1995-07-19	Wellcome Found	Therapeuticaly active compounds

2000
- 2000-03-01 FI FI20000480A patent/FI20000480A0/fi unknown
2001
- 2001-02-28 AU AU2001239331A patent/AU2001239331A1/en not_active Abandoned
- 2001-02-28 RU RU2002125944/04A patent/RU2002125944A/ru not_active Application Discontinuation
- 2001-02-28 EE EEP200200490A patent/EE200200490A/et unknown
- 2001-02-28 HU HU0204458A patent/HUP0204458A3/hu unknown
- 2001-02-28 KR KR1020027011453A patent/KR20020089372A/ko not_active Application Discontinuation
- 2001-02-28 IL IL15109301A patent/IL151093A0/xx unknown
- 2001-02-28 MX MXPA02008402A patent/MXPA02008402A/es unknown
- 2001-02-28 CA CA002400657A patent/CA2400657A1/en not_active Abandoned
- 2001-02-28 BR BR0108816-5A patent/BR0108816A/pt not_active Application Discontinuation
- 2001-02-28 PL PL01357874A patent/PL357874A1/xx not_active Application Discontinuation
- 2001-02-28 CN CNA018059236A patent/CN1468224A/zh active Pending
- 2001-02-28 SK SK1233-2002A patent/SK12332002A3/sk unknown
- 2001-02-28 JP JP2001563488A patent/JP2003525274A/ja active Pending
- 2001-02-28 WO PCT/FI2001/000203 patent/WO2001064645A2/en not_active Application Discontinuation
- 2001-02-28 EP EP01913918A patent/EP1263733A2/en not_active Withdrawn
- 2001-02-28 CZ CZ20022880A patent/CZ20022880A3/cs unknown
- 2001-03-01 AR ARP010100993A patent/AR034249A1/es unknown
- 2001-03-01 PE PE2001000208A patent/PE20011084A1/es not_active Application Discontinuation
2002
- 2002-08-29 ZA ZA200206956A patent/ZA200206956B/en unknown
- 2002-08-30 NO NO20024159A patent/NO20024159D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
SK12332002A3 (sk)	2003-07-01
WO2001064645A3 (en)	2001-12-27
IL151093A0 (en)	2003-04-10
PE20011084A1 (es)	2001-10-25
WO2001064645A2 (en)	2001-09-07
JP2003525274A (ja)	2003-08-26
FI20000480A0 (fi)	2000-03-01
PL357874A1 (en)	2004-07-26
RU2002125944A (ru)	2004-02-27
BR0108816A (pt)	2002-12-10
EE200200490A (et)	2003-12-15
CN1468224A (zh)	2004-01-14
HUP0204458A3 (en)	2004-07-28
AR034249A1 (es)	2004-02-18
HUP0204458A2 (hu)	2003-04-28
NO20024159L (no)	2002-08-30
MXPA02008402A (es)	2003-10-14
KR20020089372A (ko)	2002-11-29
ZA200206956B (en)	2003-12-01
EP1263733A2 (en)	2002-12-11
CA2400657A1 (en)	2001-09-07
CZ20022880A3 (cs)	2003-06-18
NO20024159D0 (no)	2002-08-30

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