OA11651A - 4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinolines as CETP inhibitors. - Google Patents

4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinolines as CETP inhibitors. Download PDF

Info

Publication number: OA11651A
Authority: OA; OAPI
Prior art keywords: alkyl; optionally; substituted; mono; trifluoromethyl
Prior art date: 1998-09-17

Application number

OA1200100062A

Other languages

English (en)

Inventor

Michael Paul Deninno

George Tetteh Magnus-Aryitey

Roger Benjamin Ruggeri

Ronald Thure Wester

Original Assignee

Pfizer Prod Inc

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.)

1998-09-17

Filing date

1999-09-10

Publication date

2004-12-07

1999-09-10 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2004-12-07 Publication of OA11651A publication Critical patent/OA11651A/en

Links

239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title abstract description 10
150000001875 compounds Chemical class 0.000 claims abstract description 390
239000000651 prodrug Substances 0.000 claims abstract description 109
229940002612 prodrug Drugs 0.000 claims abstract description 109
241000124008 Mammalia Species 0.000 claims abstract description 68
239000003112 inhibitor Substances 0.000 claims abstract description 59
150000003839 salts Chemical class 0.000 claims abstract description 27
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 24
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 270
-1 (C1-C4)aikylthio Chemical group 0.000 claims description 171
229920006395 saturated elastomer Polymers 0.000 claims description 171
125000000217 alkyl group Chemical group 0.000 claims description 143
229910052757 nitrogen Inorganic materials 0.000 claims description 140
229910052717 sulfur Inorganic materials 0.000 claims description 122
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 119
239000011593 sulfur Substances 0.000 claims description 119
229910052760 oxygen Inorganic materials 0.000 claims description 114
239000001301 oxygen Substances 0.000 claims description 112
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 111
125000004043 oxo group Chemical group O=* 0.000 claims description 107
125000001153 fluoro group Chemical group F* 0.000 claims description 92
235000019000 fluorine Nutrition 0.000 claims description 90
125000005842 heteroatom Chemical group 0.000 claims description 90
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 86
125000001424 substituent group Chemical group 0.000 claims description 85
150000002148 esters Chemical class 0.000 claims description 77
125000003545 alkoxy group Chemical group 0.000 claims description 75
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 73
229910052799 carbon Inorganic materials 0.000 claims description 63
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 63
239000000203 mixture Substances 0.000 claims description 60
239000002253 acid Substances 0.000 claims description 50
238000011282 treatment Methods 0.000 claims description 50
241000282414 Homo sapiens Species 0.000 claims description 45
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 45
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims description 44
125000004093 cyano group Chemical group *C#N 0.000 claims description 43
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 33
125000004414 alkyl thio group Chemical group 0.000 claims description 32
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125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 21
239000001257 hydrogen Substances 0.000 claims description 20
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
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125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
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229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 15
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125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 13
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
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125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 9
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PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
125000002619 bicyclic group Chemical group 0.000 claims description 8
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QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 7
ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 7
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PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 7
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RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 7
239000003613 bile acid Substances 0.000 claims description 7
229940125753 fibrate Drugs 0.000 claims description 7
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239000003456 ion exchange resin Substances 0.000 claims description 7
229920003303 ion-exchange polymer Polymers 0.000 claims description 7
229960004844 lovastatin Drugs 0.000 claims description 7
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 7
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 7
229960002965 pravastatin Drugs 0.000 claims description 7
TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 7
125000004076 pyridyl group Chemical group 0.000 claims description 7
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RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 7
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 6
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
239000003963 antioxidant agent Substances 0.000 claims description 6
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GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 claims description 6
239000002552 dosage form Substances 0.000 claims description 6
230000001225 therapeutic effect Effects 0.000 claims description 6
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 5
238000010521 absorption reaction Methods 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
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125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
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238000004519 manufacturing process Methods 0.000 claims description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
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125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
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PJJDKSLBOOCAKM-QUCCMNQESA-N propan-2-yl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound N([C@H]1C[C@H](N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PJJDKSLBOOCAKM-QUCCMNQESA-N 0.000 claims description 2
IKKBFQQGQVJFHF-UHFFFAOYSA-N propan-2-yl 4-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-(methoxymethyl)-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C12=CC(C(F)(F)F)=CC=C2N(C(=O)OC(C)C)C(COC)CC1N(C(C)=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IKKBFQQGQVJFHF-UHFFFAOYSA-N 0.000 claims description 2
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HAHWMWQEXPGSCY-SKDRFNHKSA-N propyl (2r,4s)-4-amino-2-methyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound FC(F)(F)C1=CC=C2N(C(=O)OCCC)[C@H](C)C[C@H](N)C2=C1 HAHWMWQEXPGSCY-SKDRFNHKSA-N 0.000 description 1
JXSVCQVXKJFVPF-UHFFFAOYSA-N propyl 4-amino-2-cyclopropyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1C(N)C2=CC(C(F)(F)F)=CC=C2N(C(=O)OCCC)C1C1CC1 JXSVCQVXKJFVPF-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000005857 pyrrolidino(C2-C3)alkyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
239000000700 radioactive tracer Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000012216 screening Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
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
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
229960002256 spironolactone Drugs 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
150000003432 sterols Chemical class 0.000 description 1
235000003702 sterols Nutrition 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
231100000057 systemic toxicity Toxicity 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
PNDGAJOEQLTMFW-UHFFFAOYSA-N tert-butyl 4-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-cyclopropyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1C(C2CC2)N(C(=O)OC(C)(C)C)C2=CC=C(C(F)(F)F)C=C2C1N(C(=O)C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PNDGAJOEQLTMFW-UHFFFAOYSA-N 0.000 description 1
AZAKMLHUDVIDFN-UHFFFAOYSA-N tert-butyl nitrate Chemical compound CC(C)(C)O[N+]([O-])=O AZAKMLHUDVIDFN-UHFFFAOYSA-N 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003777 thiepinyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
210000000115 thoracic cavity Anatomy 0.000 description 1
238000004448 titration Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000002627 tracheal intubation Methods 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
239000006211 transdermal dosage form Substances 0.000 description 1
230000007704 transition Effects 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
NAWZSHBMUXXTGV-UHFFFAOYSA-M triethyl(hexyl)azanium;bromide Chemical compound [Br-].CCCCCC[N+](CC)(CC)CC NAWZSHBMUXXTGV-UHFFFAOYSA-M 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
238000005199 ultracentrifugation Methods 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1
229930188494 zaragozic acid Natural products 0.000 description 1
DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
150000003952 β-lactams Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- 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
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- A61P9/12—Antihypertensives
- 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
- 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
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
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Chemical Kinetics & Catalysis (AREA)
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Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Hematology (AREA)
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Urology & Nephrology (AREA)
Child & Adolescent Psychology (AREA)
Vascular Medicine (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

OA1200100062A 1998-09-17 1999-09-10 4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinolines as CETP inhibitors. OA11651A (en)

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Application Number	Priority Date	Filing Date	Title
US10092798P	1998-09-17	1998-09-17

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Publication Number	Publication Date
OA11651A true OA11651A (en)	2004-12-07

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US (2)	US6140343A (es)
EP (1)	EP1114032B1 (es)
JP (1)	JP3561474B2 (es)
KR (1)	KR100422286B1 (es)
CN (2)	CN1318057A (es)
AP (1)	AP1345A (es)
AR (1)	AR030523A1 (es)
AT (1)	ATE268324T1 (es)
AU (1)	AU747715B2 (es)
BG (1)	BG65101B1 (es)
BR (1)	BR9913855A (es)
CA (1)	CA2344248C (es)
CO (1)	CO5290250A1 (es)
CR (1)	CR6306A (es)
CU (1)	CU23053A3 (es)
CZ (1)	CZ2001954A3 (es)
DE (1)	DE69917790T2 (es)
DK (1)	DK1114032T3 (es)
DZ (1)	DZ2891A1 (es)
EA (1)	EA005761B1 (es)
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GC (1)	GC0000108A (es)
GE (1)	GEP20032973B (es)
GT (1)	GT199900147A (es)
HK (1)	HK1039938A1 (es)
HR (1)	HRP20010200B1 (es)
HU (1)	HUP0103512A3 (es)
ID (1)	ID27838A (es)
IL (1)	IL141388A0 (es)
IS (1)	IS2278B (es)
MA (1)	MA26689A1 (es)
MY (1)	MY121405A (es)
NO (1)	NO319781B1 (es)
NZ (1)	NZ509837A (es)
OA (1)	OA11651A (es)
PA (1)	PA8481201A1 (es)
PE (1)	PE20001054A1 (es)
PL (1)	PL198124B1 (es)
PT (1)	PT1114032E (es)
SI (1)	SI1114032T1 (es)
SK (1)	SK3532001A3 (es)
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TN (1)	TNSN99170A1 (es)
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Publication number	Publication date
EP1114032B1 (en)	2004-06-02
UA70960C2 (uk)	2004-11-15
BG105429A (en)	2001-12-29
HRP20010200A2 (en)	2002-04-30
GEP20032973B (en)	2003-05-27
CA2344248A1 (en)	2000-03-30
HUP0103512A3 (en)	2002-03-28
DE69917790D1 (de)	2004-07-08
NZ509837A (en)	2002-11-26
PT1114032E (pt)	2004-09-30
GT199900147A (es)	1999-09-06
DK1114032T3 (da)	2004-08-16
ES2221420T3 (es)	2004-12-16
PA8481201A1 (es)	2000-09-29
CR6306A (es)	2003-08-28
YU18101A (sh)	2004-05-12
BR9913855A (pt)	2001-07-24
US6140343A (en)	2000-10-31
AU747715B2 (en)	2002-05-23
KR20010085814A (ko)	2001-09-07
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Publication	Publication Date	Title
US6140343A (en)	2000-10-31	4-amino substituted-2-substituted-1,2,3,4-tetrahydroquinolines
AU752566B2 (en)	2002-09-19	4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines as CETP inhibitors
US6147090A (en)	2000-11-14	4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines
EP0992496B1 (en)	2005-08-10	Annulated 4-carboxyamino-2-methyl-1,2,3,4-tetrahydroquinolines as CETP inhibitors
US6140342A (en)	2000-10-31	Oxy substituted 4-carboxyamino-2-methyl-1,2,3,4-tetrahydroquinolines
AU775607B2 (en)	2004-08-05	4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines as CETP inhibitors
EP1607389A1 (en)	2005-12-21	4-protected-amino-2-substituted-1,2,3,4-tetrahydroquinolines as intermediates for CETP inhibitors
MXPA01002880A (es)	2001-12-04	1,2,3,4-tetrahidroquinolinas 2-sustituidas 4-amino sustituidas como inhibidores de proteina de transferencia de ester colesterilico
MXPA01002753A (es)	2001-11-21	4-carboxiamino-2-metil-1,2,3,4-tetrahidroquinolinas como inhibidores de la proteina de transferencia del ester colesterilico