NO312028B1 - 4-substituerte piperidinanaloger - Google Patents
4-substituerte piperidinanaloger Download PDFInfo
- Publication number
- NO312028B1 NO312028B1 NO19982869A NO982869A NO312028B1 NO 312028 B1 NO312028 B1 NO 312028B1 NO 19982869 A NO19982869 A NO 19982869A NO 982869 A NO982869 A NO 982869A NO 312028 B1 NO312028 B1 NO 312028B1
- Authority
- NO
- Norway
- Prior art keywords
- butynyl
- benzyl
- phenyl
- piperidine
- group
- Prior art date
Links
- -1 4-substituted piperidine Chemical class 0.000 title claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 20
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 10
- 208000002193 Pain Diseases 0.000 claims abstract description 10
- 206010010904 Convulsion Diseases 0.000 claims abstract description 9
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 9
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 9
- 208000006011 Stroke Diseases 0.000 claims abstract description 9
- 230000036506 anxiety Effects 0.000 claims abstract description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 9
- 208000000094 Chronic Pain Diseases 0.000 claims abstract description 7
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 7
- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 6
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 6
- 208000013016 Hypoglycemia Diseases 0.000 claims abstract description 6
- 230000002218 hypoglycaemic effect Effects 0.000 claims abstract description 6
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 claims abstract description 5
- 206010027603 Migraine headaches Diseases 0.000 claims abstract description 5
- 208000001763 cytomegalovirus retinitis Diseases 0.000 claims abstract description 5
- 206010011878 Deafness Diseases 0.000 claims abstract description 4
- 230000010370 hearing loss Effects 0.000 claims abstract description 4
- 231100000888 hearing loss Toxicity 0.000 claims abstract description 4
- 208000016354 hearing loss disease Diseases 0.000 claims abstract description 4
- 208000001738 Nervous System Trauma Diseases 0.000 claims abstract description 3
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 3
- 230000036461 convulsion Effects 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 118
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 45
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 36
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 30
- 150000002431 hydrogen Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 16
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 16
- 125000001041 indolyl group Chemical group 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004043 oxo group Chemical group O=* 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 10
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 230000004770 neurodegeneration Effects 0.000 claims description 10
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 9
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 claims description 9
- IPHNHHOINYUNHW-UHFFFAOYSA-N 4-benzyl-1-but-3-ynylpiperidine Chemical compound C1CN(CCC#C)CCC1CC1=CC=CC=C1 IPHNHHOINYUNHW-UHFFFAOYSA-N 0.000 claims description 8
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- 238000006478 transmetalation reaction Methods 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
- KOOZXZDEBFUPRI-UHFFFAOYSA-N 1-but-3-ynyl-4-(4-chlorophenyl)piperidin-4-ol Chemical compound C=1C=C(Cl)C=CC=1C1(O)CCN(CCC#C)CC1 KOOZXZDEBFUPRI-UHFFFAOYSA-N 0.000 claims description 6
- CZBDUSALKFUNTF-UHFFFAOYSA-N 1-but-3-ynyl-4-[(4-chlorophenyl)methyl]piperidine Chemical compound C1=CC(Cl)=CC=C1CC1CCN(CCC#C)CC1 CZBDUSALKFUNTF-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- ISVKCDBNGIPSLZ-UHFFFAOYSA-N 1-[4-(4-aminophenyl)but-3-ynyl]-4-benzylpiperidin-4-ol Chemical compound C1=CC(N)=CC=C1C#CCCN1CCC(O)(CC=2C=CC=CC=2)CC1 ISVKCDBNGIPSLZ-UHFFFAOYSA-N 0.000 claims description 5
- RFZQVGCGPXJANP-UHFFFAOYSA-N 3-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]aniline Chemical compound NC1=CC=CC(C#CCCN2CCC(CC=3C=CC=CC=3)CC2)=C1 RFZQVGCGPXJANP-UHFFFAOYSA-N 0.000 claims description 5
- SYYKYYJFGJHYGB-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 SYYKYYJFGJHYGB-UHFFFAOYSA-N 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- PDBVBEUUEWBWHA-UHFFFAOYSA-N 1-[4-(3-aminophenyl)but-3-ynyl]-4-(4-chlorophenyl)piperidin-4-ol Chemical compound NC1=CC=CC(C#CCCN2CCC(O)(CC2)C=2C=CC(Cl)=CC=2)=C1 PDBVBEUUEWBWHA-UHFFFAOYSA-N 0.000 claims description 4
- QRJZGVVKGFIGLI-UHFFFAOYSA-N 2-phenylguanidine Chemical compound NC(=N)NC1=CC=CC=C1 QRJZGVVKGFIGLI-UHFFFAOYSA-N 0.000 claims description 4
- VTDNMOIPAWUQFC-UHFFFAOYSA-N 4-[4-[4-[(4-chlorophenyl)methyl]piperidin-1-yl]but-1-ynyl]aniline Chemical compound C1=CC(N)=CC=C1C#CCCN1CCC(CC=2C=CC(Cl)=CC=2)CC1 VTDNMOIPAWUQFC-UHFFFAOYSA-N 0.000 claims description 4
- JNMBUZAZEDOCAV-UHFFFAOYSA-N 4-benzyl-1-but-3-ynylpiperidin-4-ol Chemical compound C=1C=CC=CC=1CC1(O)CCN(CCC#C)CC1 JNMBUZAZEDOCAV-UHFFFAOYSA-N 0.000 claims description 4
- VSRIYVIORLQEQY-UHFFFAOYSA-N 4-phenyl-1-(4-phenylbut-3-ynyl)piperidine Chemical compound C=1C=CC=CC=1C#CCCN(CC1)CCC1C1=CC=CC=C1 VSRIYVIORLQEQY-UHFFFAOYSA-N 0.000 claims description 4
- ILABISIOLQXNHJ-UHFFFAOYSA-N 5-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-1h-indole Chemical compound C=1C=C2NC=CC2=CC=1C#CCCN(CC1)CCC1CC1=CC=CC=C1 ILABISIOLQXNHJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 claims description 4
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- SLUSUHNSAJADBJ-UHFFFAOYSA-N 1-(4-phenylbut-3-ynyl)-4-[3-(trifluoromethyl)phenyl]piperidin-3-ol Chemical compound C1CC(C=2C=C(C=CC=2)C(F)(F)F)C(O)CN1CCC#CC1=CC=CC=C1 SLUSUHNSAJADBJ-UHFFFAOYSA-N 0.000 claims description 3
- XQAQHAILWBQCJU-UHFFFAOYSA-N 1-[4-(4-aminophenyl)but-3-ynyl]-4-(4-chlorophenyl)piperidin-4-ol Chemical compound C1=CC(N)=CC=C1C#CCCN1CCC(O)(C=2C=CC(Cl)=CC=2)CC1 XQAQHAILWBQCJU-UHFFFAOYSA-N 0.000 claims description 3
- ZITZUKAOCKEMQS-UHFFFAOYSA-N 3-[4-[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]but-1-ynyl]aniline Chemical compound NC1=CC=CC(C#CCCN2CC=C(CC2)C=2C=CC(Cl)=CC=2)=C1 ZITZUKAOCKEMQS-UHFFFAOYSA-N 0.000 claims description 3
- KSAODGRRVYJNHC-UHFFFAOYSA-N 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]aniline Chemical compound C1=CC(N)=CC=C1C#CCN1CCC(CC=2C=CC=CC=2)CC1 KSAODGRRVYJNHC-UHFFFAOYSA-N 0.000 claims description 3
- ZEJPSKOWVYBQHM-UHFFFAOYSA-N 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C#CCN1CCC(CC=2C=CC=CC=2)CC1 ZEJPSKOWVYBQHM-UHFFFAOYSA-N 0.000 claims description 3
- RTNDIYAWRAEQKB-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-2-nitroaniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 RTNDIYAWRAEQKB-UHFFFAOYSA-N 0.000 claims description 3
- COTXHBXDTNKBKW-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 COTXHBXDTNKBKW-UHFFFAOYSA-N 0.000 claims description 3
- YFYRNQJYAUAGBK-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-n-butylbenzamide Chemical compound C1=CC(C(=O)NCCCC)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 YFYRNQJYAUAGBK-UHFFFAOYSA-N 0.000 claims description 3
- LQHMXMOZTNJDHD-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-n-methylaniline Chemical compound C1=CC(NC)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 LQHMXMOZTNJDHD-UHFFFAOYSA-N 0.000 claims description 3
- VIOYTEZUBLWNPQ-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 VIOYTEZUBLWNPQ-UHFFFAOYSA-N 0.000 claims description 3
- DQZBYMUDSJTGLY-UHFFFAOYSA-N 4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]phenol Chemical compound C1=CC(O)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 DQZBYMUDSJTGLY-UHFFFAOYSA-N 0.000 claims description 3
- VBQOHGITPGAJDD-UHFFFAOYSA-N 4-[4-[4-(4-chlorophenoxy)piperidin-1-yl]but-1-ynyl]aniline Chemical compound C1=CC(N)=CC=C1C#CCCN1CCC(OC=2C=CC(Cl)=CC=2)CC1 VBQOHGITPGAJDD-UHFFFAOYSA-N 0.000 claims description 3
- SFDSSPBJYBMRGW-UHFFFAOYSA-N 4-[4-[4-[(4-chlorophenyl)methyl]piperidin-1-yl]but-1-ynyl]-2-fluoroaniline Chemical compound C1=C(F)C(N)=CC=C1C#CCCN1CCC(CC=2C=CC(Cl)=CC=2)CC1 SFDSSPBJYBMRGW-UHFFFAOYSA-N 0.000 claims description 3
- YRFCOODQNSADOY-UHFFFAOYSA-N 4-[4-[4-[(4-methylphenyl)methyl]piperidin-1-yl]but-1-ynyl]phenol Chemical compound C1=CC(C)=CC=C1CC1CCN(CCC#CC=2C=CC(O)=CC=2)CC1 YRFCOODQNSADOY-UHFFFAOYSA-N 0.000 claims description 3
- SCAISMIQJWDCGC-UHFFFAOYSA-N 4-benzyl-1-(4-phenylbut-3-ynyl)piperidin-4-ol Chemical compound C1CN(CCC#CC=2C=CC=CC=2)CCC1(O)CC1=CC=CC=C1 SCAISMIQJWDCGC-UHFFFAOYSA-N 0.000 claims description 3
- JKHKJUWIHNVFFI-UHFFFAOYSA-N 4-benzyl-1-(4-phenylbut-3-ynyl)piperidine Chemical compound C=1C=CC=CC=1C#CCCN(CC1)CCC1CC1=CC=CC=C1 JKHKJUWIHNVFFI-UHFFFAOYSA-N 0.000 claims description 3
- QZCFWXKDDJAIKH-UHFFFAOYSA-N 4-benzyl-1-[4-(3-chlorophenyl)but-3-ynyl]piperidine Chemical compound ClC1=CC=CC(C#CCCN2CCC(CC=3C=CC=CC=3)CC2)=C1 QZCFWXKDDJAIKH-UHFFFAOYSA-N 0.000 claims description 3
- TYZGRLKUJKJAPY-UHFFFAOYSA-N 4-benzyl-1-[4-(3-methylphenyl)but-3-ynyl]piperidine Chemical compound CC1=CC=CC(C#CCCN2CCC(CC=3C=CC=CC=3)CC2)=C1 TYZGRLKUJKJAPY-UHFFFAOYSA-N 0.000 claims description 3
- VBQGLKVYZYVDKA-UHFFFAOYSA-N 4-benzyl-1-[4-(4-chlorophenyl)but-3-ynyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 VBQGLKVYZYVDKA-UHFFFAOYSA-N 0.000 claims description 3
- IPSPEWKFMKDKSD-UHFFFAOYSA-N 4-benzyl-1-[4-(4-fluorophenyl)but-3-ynyl]piperidine Chemical compound C1=CC(F)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 IPSPEWKFMKDKSD-UHFFFAOYSA-N 0.000 claims description 3
- VVYCKPKSEYDOAF-UHFFFAOYSA-N 4-benzyl-1-[4-(4-methoxyphenyl)but-3-ynyl]piperidine Chemical compound C1=CC(OC)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 VVYCKPKSEYDOAF-UHFFFAOYSA-N 0.000 claims description 3
- XBGIMQCGDSYYIA-UHFFFAOYSA-N 4-benzyl-1-[4-(4-methylphenyl)but-3-ynyl]piperidine Chemical compound C1=CC(C)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 XBGIMQCGDSYYIA-UHFFFAOYSA-N 0.000 claims description 3
- WKOIWFDPOLFHOG-UHFFFAOYSA-N 4-benzyl-1-[4-(4-nitrophenyl)but-3-ynyl]piperidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 WKOIWFDPOLFHOG-UHFFFAOYSA-N 0.000 claims description 3
- JTHIYPHEWHYVLG-UHFFFAOYSA-N 5-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-1h-indazole Chemical compound C=1C=C2NN=CC2=CC=1C#CCCN(CC1)CCC1CC1=CC=CC=C1 JTHIYPHEWHYVLG-UHFFFAOYSA-N 0.000 claims description 3
- AXUWVXZRYBGRBW-UHFFFAOYSA-N 5-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]-1h-indole-2,3-dione Chemical compound C1=C2C(=O)C(=O)NC2=CC=C1C#CCCN(CC1)CCC1CC1=CC=CC=C1 AXUWVXZRYBGRBW-UHFFFAOYSA-N 0.000 claims description 3
- JRBBEWSIXBWGPM-UHFFFAOYSA-N [3-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]phenyl]methanamine Chemical compound NCC1=CC=CC(C#CCCN2CCC(CC=3C=CC=CC=3)CC2)=C1 JRBBEWSIXBWGPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- XUIIEFRDBMIDAY-UHFFFAOYSA-N n-[4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C#CCN1CCC(CC=2C=CC=CC=2)CC1 XUIIEFRDBMIDAY-UHFFFAOYSA-N 0.000 claims description 3
- RZOQAAQWMIFUOZ-UHFFFAOYSA-N n-[4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C#CCCN1CCC(CC=2C=CC=CC=2)CC1 RZOQAAQWMIFUOZ-UHFFFAOYSA-N 0.000 claims description 3
- XNRMQSSRCDZSCB-UHFFFAOYSA-N n-[4-[4-(4-phenoxypiperidin-1-yl)but-1-ynyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C#CCCN1CCC(OC=2C=CC=CC=2)CC1 XNRMQSSRCDZSCB-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- CGHQVSFNAMZXPY-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)but-3-ynyl]-4-benzylpiperidine Chemical compound C=1C=C2OCOC2=CC=1C#CCCN(CC1)CCC1CC1=CC=CC=C1 CGHQVSFNAMZXPY-UHFFFAOYSA-N 0.000 claims description 2
- NWBGTSNKOYVTRT-UHFFFAOYSA-N 1-[4-(3-aminophenyl)but-3-ynyl]-4-benzylpiperidin-3-ol Chemical compound NC1=CC=CC(C#CCCN2CC(O)C(CC=3C=CC=CC=3)CC2)=C1 NWBGTSNKOYVTRT-UHFFFAOYSA-N 0.000 claims description 2
- FUWSTCSPLGEKOM-UHFFFAOYSA-N 1-[4-(3-aminophenyl)but-3-ynyl]-n-(4-chlorophenyl)piperidin-4-amine Chemical compound NC1=CC=CC(C#CCCN2CCC(CC2)NC=2C=CC(Cl)=CC=2)=C1 FUWSTCSPLGEKOM-UHFFFAOYSA-N 0.000 claims description 2
- GYXQIQUDONKGID-UHFFFAOYSA-N 1-[4-(4-aminophenyl)but-3-ynyl]-4-[(4-methylphenyl)methyl]piperidin-4-ol Chemical compound C1=CC(C)=CC=C1CC1(O)CCN(CCC#CC=2C=CC(N)=CC=2)CC1 GYXQIQUDONKGID-UHFFFAOYSA-N 0.000 claims description 2
- YFALZLZSGFNKFB-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)but-3-ynyl]-4-[[3-(trifluoromethyl)phenyl]methyl]piperidin-3-ol Chemical compound C1CC(CC=2C=C(C=CC=2)C(F)(F)F)C(O)CN1CCC#CC1=CC=C(F)C=C1 YFALZLZSGFNKFB-UHFFFAOYSA-N 0.000 claims description 2
- XQXBTRPARQNLEB-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)but-3-ynyl]-4-[[3-(trifluoromethyl)phenyl]methyl]piperidine Chemical compound C1=CC(F)=CC=C1C#CCCN1CCC(CC=2C=C(C=CC=2)C(F)(F)F)CC1 XQXBTRPARQNLEB-UHFFFAOYSA-N 0.000 claims description 2
- ROVIIYKQKCRXCA-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)but-3-ynyl]-n-[3-(trifluoromethyl)phenyl]piperidin-4-amine Chemical compound C1=CC(F)=CC=C1C#CCCN1CCC(NC=2C=C(C=CC=2)C(F)(F)F)CC1 ROVIIYKQKCRXCA-UHFFFAOYSA-N 0.000 claims description 2
- MDVYAYYFUIREDQ-UHFFFAOYSA-N 1-[5-(3-aminophenyl)pent-4-ynyl]-4-(4-chlorophenyl)piperidin-4-ol Chemical compound NC1=CC=CC(C#CCCCN2CCC(O)(CC2)C=2C=CC(Cl)=CC=2)=C1 MDVYAYYFUIREDQ-UHFFFAOYSA-N 0.000 claims description 2
- MQDOBFZXCPBKQH-UHFFFAOYSA-N 1-[5-(3-aminophenyl)pent-4-ynyl]-4-[(4-chlorophenyl)methyl]piperidin-3-ol Chemical compound NC1=CC=CC(C#CCCCN2CC(O)C(CC=3C=CC(Cl)=CC=3)CC2)=C1 MQDOBFZXCPBKQH-UHFFFAOYSA-N 0.000 claims description 2
- LNKNRUPHEAODHR-UHFFFAOYSA-N 1-but-3-ynyl-4-phenoxypiperidine Chemical compound C1CN(CCC#C)CCC1OC1=CC=CC=C1 LNKNRUPHEAODHR-UHFFFAOYSA-N 0.000 claims description 2
- BUVFBRJIQSNMSQ-UHFFFAOYSA-N 1-but-3-ynyl-4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCN(CCC#C)CC1 BUVFBRJIQSNMSQ-UHFFFAOYSA-N 0.000 claims description 2
- KEXNAWIGILECRE-UHFFFAOYSA-N 1-but-3-ynyl-n-(4-chlorophenyl)piperidin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC1CCN(CCC#C)CC1 KEXNAWIGILECRE-UHFFFAOYSA-N 0.000 claims description 2
- GVGNYBYGPXNXMA-UHFFFAOYSA-N 1-but-3-ynyl-n-phenylpiperidin-4-amine Chemical compound C1CN(CCC#C)CCC1NC1=CC=CC=C1 GVGNYBYGPXNXMA-UHFFFAOYSA-N 0.000 claims description 2
- CAAAMJAVWLMHOQ-UHFFFAOYSA-N 1-pent-4-ynyl-4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCN(CCCC#C)CC1 CAAAMJAVWLMHOQ-UHFFFAOYSA-N 0.000 claims description 2
- UAZSCOFMJCDPOP-UHFFFAOYSA-N 2-[4-(4-phenylpiperidin-1-yl)but-1-ynyl]aniline Chemical compound NC1=CC=CC=C1C#CCCN1CCC(C=2C=CC=CC=2)CC1 UAZSCOFMJCDPOP-UHFFFAOYSA-N 0.000 claims description 2
- MCILTFLACBDPGR-UHFFFAOYSA-N 3-[4-(4-phenoxypiperidin-1-yl)but-1-ynyl]aniline Chemical compound NC1=CC=CC(C#CCCN2CCC(CC2)OC=2C=CC=CC=2)=C1 MCILTFLACBDPGR-UHFFFAOYSA-N 0.000 claims description 2
- VVLYRAXDDLNGFE-UHFFFAOYSA-N 3-[5-[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]pent-1-ynyl]aniline Chemical compound NC1=CC=CC(C#CCCCN2CC=C(CC2)C=2C=CC(Cl)=CC=2)=C1 VVLYRAXDDLNGFE-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- 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
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- A—HUMAN NECESSITIES
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- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/54—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US919295P | 1995-12-22 | 1995-12-22 | |
PCT/US1996/020766 WO1997023214A1 (en) | 1995-12-22 | 1996-12-20 | 4-substituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
Publications (3)
Publication Number | Publication Date |
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NO982869D0 NO982869D0 (no) | 1998-06-19 |
NO982869L NO982869L (no) | 1998-08-24 |
NO312028B1 true NO312028B1 (no) | 2002-03-04 |
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NO19982869A NO312028B1 (no) | 1995-12-22 | 1998-06-19 | 4-substituerte piperidinanaloger |
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US (4) | US6130234A (cs) |
EP (1) | EP0869791B1 (cs) |
JP (1) | JP2000502352A (cs) |
AT (1) | ATE239473T1 (cs) |
AU (1) | AU719430B2 (cs) |
BG (1) | BG63424B1 (cs) |
BR (1) | BR9612153A (cs) |
CA (1) | CA2240038A1 (cs) |
CZ (1) | CZ177898A3 (cs) |
DE (1) | DE69628035T2 (cs) |
DK (1) | DK0869791T3 (cs) |
EA (1) | EA001133B1 (cs) |
ES (1) | ES2196196T3 (cs) |
IL (1) | IL125060A (cs) |
MX (1) | MX9805032A (cs) |
NO (1) | NO312028B1 (cs) |
NZ (1) | NZ325735A (cs) |
PL (1) | PL327413A1 (cs) |
PT (1) | PT869791E (cs) |
SK (1) | SK82398A3 (cs) |
WO (1) | WO1997023214A1 (cs) |
ZA (1) | ZA9610741B (cs) |
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ZA9610736B (en) * | 1995-12-22 | 1997-06-27 | Warner Lambert Co | 2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists |
WO1998010757A2 (en) * | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | The use of functional n-methyl-d-aspartate antagonists to ameliorate or prevent aminoglycoside-induced ototoxicity |
GB9704948D0 (en) * | 1997-03-11 | 1997-04-30 | Knoll Ag | Therapeutic agents |
HUP0004900A3 (en) | 1997-10-24 | 2002-03-28 | Warner Lambert Co | Pharmaceutical compositions for treating disease-related or drug-induced dyskinesias containing piperidine derivatives as nmda receptor antagonist as active ingredient |
US6960577B2 (en) * | 1998-05-22 | 2005-11-01 | Eli Lilly And Company | Combination therapy for treatment of refractory depression |
PE20000728A1 (es) * | 1998-06-26 | 2000-08-21 | Cocensys Inc | Heterociclos 4-bencil piperidina alquilsulfoxido y su uso como antagonistas receptores subtipo-selectivo nmda |
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1996
- 1996-12-19 ZA ZA9610741A patent/ZA9610741B/xx unknown
- 1996-12-20 ES ES96944537T patent/ES2196196T3/es not_active Expired - Lifetime
- 1996-12-20 EA EA199800591A patent/EA001133B1/ru not_active IP Right Cessation
- 1996-12-20 CZ CZ981778A patent/CZ177898A3/cs unknown
- 1996-12-20 US US09/091,594 patent/US6130234A/en not_active Expired - Fee Related
- 1996-12-20 SK SK823-98A patent/SK82398A3/sk unknown
- 1996-12-20 NZ NZ325735A patent/NZ325735A/en unknown
- 1996-12-20 AU AU14310/97A patent/AU719430B2/en not_active Ceased
- 1996-12-20 AT AT96944537T patent/ATE239473T1/de not_active IP Right Cessation
- 1996-12-20 DK DK96944537T patent/DK0869791T3/da active
- 1996-12-20 EP EP96944537A patent/EP0869791B1/en not_active Expired - Lifetime
- 1996-12-20 PT PT96944537T patent/PT869791E/pt unknown
- 1996-12-20 PL PL96327413A patent/PL327413A1/xx unknown
- 1996-12-20 CA CA002240038A patent/CA2240038A1/en not_active Abandoned
- 1996-12-20 WO PCT/US1996/020766 patent/WO1997023214A1/en not_active Application Discontinuation
- 1996-12-20 JP JP09523881A patent/JP2000502352A/ja not_active Ceased
- 1996-12-20 IL IL12506096A patent/IL125060A/xx not_active IP Right Cessation
- 1996-12-20 BR BR9612153-0A patent/BR9612153A/pt not_active Application Discontinuation
- 1996-12-20 DE DE69628035T patent/DE69628035T2/de not_active Expired - Fee Related
-
1998
- 1998-06-19 MX MX9805032A patent/MX9805032A/es not_active IP Right Cessation
- 1998-06-19 NO NO19982869A patent/NO312028B1/no unknown
- 1998-06-19 BG BG102561A patent/BG63424B1/bg unknown
-
2000
- 2000-06-13 US US09/592,883 patent/US6448270B1/en not_active Expired - Fee Related
-
2002
- 2002-07-29 US US10/206,578 patent/US20030105133A1/en not_active Abandoned
- 2002-08-06 US US10/172,525 patent/US20030100018A1/en not_active Abandoned
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US20030100018A1 (en) | 2003-05-29 |
AU1431097A (en) | 1997-07-17 |
DE69628035D1 (de) | 2003-06-12 |
EP0869791A1 (en) | 1998-10-14 |
ES2196196T3 (es) | 2003-12-16 |
CZ177898A3 (cs) | 1998-12-16 |
IL125060A0 (en) | 1999-01-26 |
ZA9610741B (en) | 1997-06-24 |
WO1997023214A1 (en) | 1997-07-03 |
DK0869791T3 (da) | 2003-06-10 |
US6130234A (en) | 2000-10-10 |
BG102561A (en) | 1999-04-30 |
JP2000502352A (ja) | 2000-02-29 |
NO982869D0 (no) | 1998-06-19 |
BG63424B1 (bg) | 2002-01-31 |
US20030105133A1 (en) | 2003-06-05 |
AU719430B2 (en) | 2000-05-11 |
CA2240038A1 (en) | 1997-07-03 |
SK82398A3 (en) | 1999-03-12 |
US6448270B1 (en) | 2002-09-10 |
PL327413A1 (en) | 1998-12-07 |
MX9805032A (es) | 1998-11-30 |
EA001133B1 (ru) | 2000-10-30 |
EP0869791B1 (en) | 2003-05-07 |
NO982869L (no) | 1998-08-24 |
EA199800591A1 (ru) | 1999-02-25 |
PT869791E (pt) | 2003-08-29 |
IL125060A (en) | 2003-07-31 |
BR9612153A (pt) | 1999-12-28 |
NZ325735A (en) | 2000-02-28 |
ATE239473T1 (de) | 2003-05-15 |
EP0869791A4 (en) | 1999-04-28 |
DE69628035T2 (de) | 2004-02-12 |
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