NO314228B1 - Inhibitorer for CETP-aktivitet og profylaktisk eller terapeutisk middel omfattende denne, forbindelse som inngår i inhibitoren, farmasöytiskpreparat omfattende forbindelsen og anvendelse av forbindelsen - Google Patents
Inhibitorer for CETP-aktivitet og profylaktisk eller terapeutisk middel omfattende denne, forbindelse som inngår i inhibitoren, farmasöytiskpreparat omfattende forbindelsen og anvendelse av forbindelsen Download PDFInfo
- Publication number
- NO314228B1 NO314228B1 NO19993869A NO993869A NO314228B1 NO 314228 B1 NO314228 B1 NO 314228B1 NO 19993869 A NO19993869 A NO 19993869A NO 993869 A NO993869 A NO 993869A NO 314228 B1 NO314228 B1 NO 314228B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- group
- isopentylcyclohexanecarbonylamino
- dimethylthiopropionate
- dichloro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 159
- 230000000694 effects Effects 0.000 title claims abstract description 40
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 239000003112 inhibitor Substances 0.000 title claims abstract description 17
- 229940124597 therapeutic agent Drugs 0.000 title claims abstract description 14
- KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 title claims abstract 7
- 102100037637 Cholesteryl ester transfer protein Human genes 0.000 title claims abstract 7
- 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 title claims abstract 7
- 230000000069 prophylactic effect Effects 0.000 title claims description 9
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 239000012453 solvate Substances 0.000 claims abstract description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
- 125000005843 halogen group Chemical group 0.000 claims abstract description 27
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 15
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 14
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 11
- 125000002252 acyl group Chemical group 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 239000000651 prodrug Substances 0.000 claims abstract description 3
- 229940002612 prodrug Drugs 0.000 claims abstract description 3
- -1 tetrahydroindanyl Chemical group 0.000 claims description 363
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
- 125000001424 substituent group Chemical group 0.000 claims description 50
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 34
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 17
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- OVRLABAFXJPIMU-UHFFFAOYSA-N 1-(2-ethylbutyl)-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CC(CC)CC)CCCCC1 OVRLABAFXJPIMU-UHFFFAOYSA-N 0.000 claims description 8
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 8
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 8
- OBWOWYBSZTURFB-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 OBWOWYBSZTURFB-UHFFFAOYSA-N 0.000 claims description 7
- GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 claims description 7
- DDZIFEIGSSYBIV-UHFFFAOYSA-N n-[2-[[2-(2,2-dimethylpropanoylamino)phenyl]disulfanyl]phenyl]-2,2-dimethylpropanamide Chemical group CC(C)(C)C(=O)NC1=CC=CC=C1SSC1=CC=CC=C1NC(=O)C(C)(C)C DDZIFEIGSSYBIV-UHFFFAOYSA-N 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- KOCJXXQFYRJDNP-UHFFFAOYSA-N CC(C)(C)C([O-])=[S+]C(C(NC(C1(CCCCC1)C1CC1)=O)=C1)=CC(Cl)=C1Cl Chemical compound CC(C)(C)C([O-])=[S+]C(C(NC(C1(CCCCC1)C1CC1)=O)=C1)=CC(Cl)=C1Cl KOCJXXQFYRJDNP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000005936 piperidyl group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- MUXPHVMMWCVOAH-UHFFFAOYSA-N CC(C)CCC1(CCCCC1)C(NC(C=CC=C1)=C1[S+]=C(C)[O-])=O Chemical compound CC(C)CCC1(CCCCC1)C(NC(C=CC=C1)=C1[S+]=C(C)[O-])=O MUXPHVMMWCVOAH-UHFFFAOYSA-N 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
- WSDMOYWCWHLBPX-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(2-sulfanylphenyl)cyclopentane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCC(C)C)CCCC1 WSDMOYWCWHLBPX-UHFFFAOYSA-N 0.000 claims description 4
- QSHCOFDJVJBWJU-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(4-methyl-2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=C(C)C=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 QSHCOFDJVJBWJU-UHFFFAOYSA-N 0.000 claims description 4
- ZUBAYESAZFWZPL-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(5-methyl-2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C(C)=CC=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 ZUBAYESAZFWZPL-UHFFFAOYSA-N 0.000 claims description 4
- SDFLVSQYLLGMKX-UHFFFAOYSA-N 1-(3-methylbutyl)-n-[2-[[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl]disulfanyl]phenyl]cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(SSC=2C(=CC=CC=2)NC(=O)C2(CCC(C)C)CCCCC2)C=1NC(=O)C1(CCC(C)C)CCCCC1 SDFLVSQYLLGMKX-UHFFFAOYSA-N 0.000 claims description 4
- WCHRXPOAPJPGEP-UHFFFAOYSA-N 1-(3-methylbutyl)-n-[2-[[2-[[1-(3-methylbutyl)cyclopentanecarbonyl]amino]phenyl]disulfanyl]phenyl]cyclopentane-1-carboxamide Chemical compound C=1C=CC=C(SSC=2C(=CC=CC=2)NC(=O)C2(CCC(C)C)CCCC2)C=1NC(=O)C1(CCC(C)C)CCCC1 WCHRXPOAPJPGEP-UHFFFAOYSA-N 0.000 claims description 4
- RPOWLQXTRJDTQA-UHFFFAOYSA-N 1-butyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCCC)CCCCC1 RPOWLQXTRJDTQA-UHFFFAOYSA-N 0.000 claims description 4
- HNJZDNMUVSELCB-UHFFFAOYSA-N 1-ethyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CC)CCCCC1 HNJZDNMUVSELCB-UHFFFAOYSA-N 0.000 claims description 4
- LRWUYINHKRXNQH-UHFFFAOYSA-N 1-methyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(C)CCCCC1 LRWUYINHKRXNQH-UHFFFAOYSA-N 0.000 claims description 4
- CPHKBJBFYKJFHT-UHFFFAOYSA-N 1-methyl-n-[2-[[2-[(1-methylcyclohexanecarbonyl)amino]phenyl]disulfanyl]phenyl]cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(SSC=2C(=CC=CC=2)NC(=O)C2(C)CCCCC2)C=1NC(=O)C1(C)CCCCC1 CPHKBJBFYKJFHT-UHFFFAOYSA-N 0.000 claims description 4
- YOTSORLUOLPCCV-UHFFFAOYSA-N 1-propan-2-yl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(C(C)C)CCCCC1 YOTSORLUOLPCCV-UHFFFAOYSA-N 0.000 claims description 4
- GIBQUYMCEXFBRU-UHFFFAOYSA-N 1-propyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCC)CCCCC1 GIBQUYMCEXFBRU-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- GHSLUZCHSFWKRE-UHFFFAOYSA-N n-(4,5-dichloro-2-sulfanylphenyl)-1-(3-methylbutyl)cyclohexane-1-carboxamide Chemical compound C=1C(Cl)=C(Cl)C=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 GHSLUZCHSFWKRE-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
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- YZQLWPMZQVHJED-UHFFFAOYSA-N 2-methylpropanethioic acid S-[2-[[[1-(2-ethylbutyl)cyclohexyl]-oxomethyl]amino]phenyl] ester Chemical compound C=1C=CC=C(SC(=O)C(C)C)C=1NC(=O)C1(CC(CC)CC)CCCCC1 YZQLWPMZQVHJED-UHFFFAOYSA-N 0.000 claims description 3
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- PDSPNLYCCFXTCN-UHFFFAOYSA-N s-(2-amino-4-methoxyphenyl) n,n-dimethylcarbamothioate Chemical compound COC1=CC=C(SC(=O)N(C)C)C(N)=C1 PDSPNLYCCFXTCN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4483697 | 1997-02-12 | ||
JP16508597 | 1997-06-05 | ||
JP10026688A JP2894445B2 (ja) | 1997-02-12 | 1998-01-23 | Cetp活性阻害剤として有効な化合物 |
PCT/JP1998/000542 WO1998035937A1 (fr) | 1997-02-12 | 1998-02-10 | Inhibiteurs de l'activite du cetp |
Publications (3)
Publication Number | Publication Date |
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NO993869D0 NO993869D0 (no) | 1999-08-11 |
NO993869L NO993869L (no) | 1999-09-23 |
NO314228B1 true NO314228B1 (no) | 2003-02-17 |
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Application Number | Title | Priority Date | Filing Date |
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NO19993869A NO314228B1 (no) | 1997-02-12 | 1999-08-11 | Inhibitorer for CETP-aktivitet og profylaktisk eller terapeutisk middel omfattende denne, forbindelse som inngår i inhibitoren, farmasöytiskpreparat omfattende forbindelsen og anvendelse av forbindelsen |
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US (6) | US6426365B1 (pt) |
EP (3) | EP1710231A1 (pt) |
JP (1) | JP2894445B2 (pt) |
KR (1) | KR100324183B1 (pt) |
CN (1) | CN100384821C (pt) |
AT (1) | ATE338029T1 (pt) |
AU (1) | AU728979B2 (pt) |
BR (1) | BRPI9807222B8 (pt) |
CA (1) | CA2280708C (pt) |
CY (1) | CY2587B2 (pt) |
CZ (1) | CZ302069B6 (pt) |
DE (1) | DE69835760T2 (pt) |
DK (1) | DK1020439T3 (pt) |
ES (1) | ES2270504T3 (pt) |
HK (1) | HK1029784A1 (pt) |
HU (1) | HU227763B1 (pt) |
ID (1) | ID22667A (pt) |
IL (2) | IL131250A (pt) |
NO (1) | NO314228B1 (pt) |
NZ (1) | NZ337122A (pt) |
PT (1) | PT1020439E (pt) |
RU (1) | RU2188631C2 (pt) |
SK (1) | SK282973B6 (pt) |
TW (1) | TW577865B (pt) |
WO (1) | WO1998035937A1 (pt) |
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1998
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1999
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2001
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2002
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2004
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2009
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