HRP20050859A2 - 1,2,4-suptituted 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydro-quinoxaline derivatives as cetp inhibitors for the treatment of atherosclerosis and obesity - Google Patents
1,2,4-suptituted 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydro-quinoxaline derivatives as cetp inhibitors for the treatment of atherosclerosis and obesityInfo
- Publication number
- HRP20050859A2 HRP20050859A2 HR20050859A HRP20050859A HRP20050859A2 HR P20050859 A2 HRP20050859 A2 HR P20050859A2 HR 20050859 A HR20050859 A HR 20050859A HR P20050859 A HRP20050859 A HR P20050859A HR P20050859 A2 HRP20050859 A2 HR P20050859A2
- Authority
- HR
- Croatia
- Prior art keywords
- trifluoromethyl
- methyl
- optionally
- bis
- substituted
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 53
- 201000001320 Atherosclerosis Diseases 0.000 title claims abstract description 31
- 208000008589 Obesity Diseases 0.000 title description 8
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title description 8
- 235000020824 obesity Nutrition 0.000 title description 8
- HORKYAIEVBUXGM-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoxaline Chemical class C1=CC=C2NCCNC2=C1 HORKYAIEVBUXGM-UHFFFAOYSA-N 0.000 title 1
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 447
- -1 HDL-cholesterol Chemical class 0.000 claims abstract description 154
- 125000001424 substituent group Chemical group 0.000 claims abstract description 30
- 241000124008 Mammalia Species 0.000 claims abstract description 26
- 208000019553 vascular disease Diseases 0.000 claims abstract description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 187
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 173
- 229910052799 carbon Inorganic materials 0.000 claims description 145
- 229920006395 saturated elastomer Polymers 0.000 claims description 138
- 229910052757 nitrogen Inorganic materials 0.000 claims description 116
- 125000004043 oxo group Chemical group O=* 0.000 claims description 101
- 229910052717 sulfur Inorganic materials 0.000 claims description 90
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 89
- 239000011593 sulfur Substances 0.000 claims description 89
- 125000005843 halogen group Chemical group 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 78
- 239000003112 inhibitor Substances 0.000 claims description 77
- 125000005842 heteroatom Chemical group 0.000 claims description 74
- 229910052760 oxygen Inorganic materials 0.000 claims description 71
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 70
- 239000001301 oxygen Substances 0.000 claims description 70
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 68
- 239000000651 prodrug Substances 0.000 claims description 63
- 229940002612 prodrug Drugs 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 56
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 55
- 235000019000 fluorine Nutrition 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 50
- 125000001153 fluoro group Chemical group F* 0.000 claims description 48
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 45
- 238000002360 preparation method Methods 0.000 claims description 44
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 40
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
- 239000003795 chemical substances by application Substances 0.000 claims description 37
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 36
- 125000004414 alkyl thio group Chemical group 0.000 claims description 34
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 208000029078 coronary artery disease Diseases 0.000 claims description 28
- 239000011347 resin Substances 0.000 claims description 27
- 229920005989 resin Polymers 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 25
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 23
- 235000001968 nicotinic acid Nutrition 0.000 claims description 23
- 239000011664 nicotinic acid Substances 0.000 claims description 23
- 229960003512 nicotinic acid Drugs 0.000 claims description 21
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 20
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 20
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 20
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 16
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 14
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 13
- 125000002619 bicyclic group Chemical group 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 12
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 11
- 239000003613 bile acid Substances 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- 230000028327 secretion Effects 0.000 claims description 11
- 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 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 10
- 206010021024 Hypolipidaemia Diseases 0.000 claims description 10
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 10
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 10
- 229940125753 fibrate Drugs 0.000 claims description 10
- 208000029498 hypoalphalipoproteinemia Diseases 0.000 claims description 10
- 150000002500 ions Chemical class 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- YVPOVOVZCOOSBQ-AXHZAXLDSA-N [(1s,3r,7s,8s,8ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2s)-2-methylbutanoate;pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1.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 YVPOVOVZCOOSBQ-AXHZAXLDSA-N 0.000 claims description 9
- 239000003963 antioxidant agent Substances 0.000 claims description 9
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229940124597 therapeutic agent Drugs 0.000 claims description 9
- 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 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 229960004844 lovastatin Drugs 0.000 claims description 8
- 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 8
- 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 8
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 7
- 229940123239 Cholesterol synthesis inhibitor Drugs 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 208000010125 myocardial infarction Diseases 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 239000003456 ion exchange resin Substances 0.000 claims description 6
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 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 5
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 5
- 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 5
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 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 5
- 229960003765 fluvastatin Drugs 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 229960002797 pitavastatin Drugs 0.000 claims description 5
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 5
- 229960002965 pravastatin Drugs 0.000 claims description 5
- 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 5
- 229960000672 rosuvastatin Drugs 0.000 claims description 5
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 5
- 229960002855 simvastatin Drugs 0.000 claims description 5
- 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 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 108010027006 Apolipoproteins B Proteins 0.000 claims description 4
- 102000018616 Apolipoproteins B Human genes 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- 229960005370 atorvastatin Drugs 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- HSHIMAZYOGBKJU-LYHRCORUSA-N ethyl (2R,4R)-4-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound CCOC(=O)N1[C@H](CC)C[C@H](c2cc(ccc12)C(F)(F)F)[C@@](O)(C(=O)OC)c1cc(cc(c1)C(F)(F)F)C(F)(F)F HSHIMAZYOGBKJU-LYHRCORUSA-N 0.000 claims description 2
- QQCDUYGLFVGVFT-ADCPOJHVSA-N ethyl (2R,4R)-4-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound CCOC(=O)N1[C@H](C)C[C@H](c2cc(OC)c(OC)cc12)[C@@](O)(C(=O)OC)c1cc(cc(c1)C(F)(F)F)C(F)(F)F QQCDUYGLFVGVFT-ADCPOJHVSA-N 0.000 claims description 2
- PCYNVJJRFCOHCW-CBJTVTONSA-N ethyl (2R,4R)-4-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound C(C)OC(=O)N1[C@@H](C[C@@H](C2=CC(=C(C=C12)OC)OC)[C@H](C(=O)OC)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C PCYNVJJRFCOHCW-CBJTVTONSA-N 0.000 claims description 2
- HSHIMAZYOGBKJU-HFJQGTKSSA-N ethyl (2R,4S)-4-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound CCOC(=O)N1[C@H](CC)C[C@@H](c2cc(ccc12)C(F)(F)F)[C@@](O)(C(=O)OC)c1cc(cc(c1)C(F)(F)F)C(F)(F)F HSHIMAZYOGBKJU-HFJQGTKSSA-N 0.000 claims description 2
- QQCDUYGLFVGVFT-ICBNKOFZSA-N ethyl (2R,4S)-4-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound CCOC(=O)N1[C@H](C)C[C@@H](c2cc(OC)c(OC)cc12)[C@@](O)(C(=O)OC)c1cc(cc(c1)C(F)(F)F)C(F)(F)F QQCDUYGLFVGVFT-ICBNKOFZSA-N 0.000 claims description 2
- ADFRGNYDGYPUDI-SLYNCCJLSA-N ethyl (2R,4S)-4-[(S)-[3,5-bis(trifluoromethyl)phenyl]-(methylamino)methyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound C(C)OC(=O)N1[C@@H](C[C@@H](C2=CC(=CC=C12)C(F)(F)F)[C@H](NC)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)CC ADFRGNYDGYPUDI-SLYNCCJLSA-N 0.000 claims description 2
- UDZDABRIRFMUQZ-ONTUJTEPSA-N ethyl (2R,4S)-4-[1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound C(C(=O)OC)(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)[C@]1([H])C[C@@H](CC)N(C(=O)OCC)C2=CC=C(C=C12)C(F)(F)F UDZDABRIRFMUQZ-ONTUJTEPSA-N 0.000 claims description 2
- MHJLQXWVYZWXMH-UZUQRXQVSA-N ethyl (2r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-2h-quinoline-1-carboxylate Chemical compound C1([C@](O)(C(=O)OC)C2=C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MHJLQXWVYZWXMH-UZUQRXQVSA-N 0.000 claims description 2
- HGHHHNRSYBLSTJ-YEBMWUKDSA-N ethyl (2r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-2h-quinoline-1-carboxylate Chemical compound C1([C@](O)(C(=O)OC)C2=C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HGHHHNRSYBLSTJ-YEBMWUKDSA-N 0.000 claims description 2
- MHJLQXWVYZWXMH-HXOBKFHXSA-N ethyl (2r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-2h-quinoline-1-carboxylate Chemical compound C1([C@@](O)(C(=O)OC)C2=C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MHJLQXWVYZWXMH-HXOBKFHXSA-N 0.000 claims description 2
- HGHHHNRSYBLSTJ-OZAJXLCCSA-N ethyl (2r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-2h-quinoline-1-carboxylate Chemical compound C1([C@@](O)(C(=O)OC)C2=C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HGHHHNRSYBLSTJ-OZAJXLCCSA-N 0.000 claims description 2
- FTSKYIJDBXFQAR-YLJYHZDGSA-N ethyl (2r)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6-(trifluoromethyl)-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](C#N)C2=C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FTSKYIJDBXFQAR-YLJYHZDGSA-N 0.000 claims description 2
- FTSKYIJDBXFQAR-XLIONFOSSA-N ethyl (2r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6-(trifluoromethyl)-2h-quinoline-1-carboxylate Chemical compound C1([C@H](C#N)C2=C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FTSKYIJDBXFQAR-XLIONFOSSA-N 0.000 claims description 2
- HSHIMAZYOGBKJU-BOCKYXSRSA-N ethyl (2r,4r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@](O)(C(=O)OC)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HSHIMAZYOGBKJU-BOCKYXSRSA-N 0.000 claims description 2
- QQCDUYGLFVGVFT-DDVPAQIKSA-N ethyl (2r,4r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@](O)(C(=O)OC)[C@@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 QQCDUYGLFVGVFT-DDVPAQIKSA-N 0.000 claims description 2
- NIKAXGSSAMPHOJ-WSTZPKSXSA-N ethyl (2r,4r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-fluoroethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](CF)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NIKAXGSSAMPHOJ-WSTZPKSXSA-N 0.000 claims description 2
- UDZDABRIRFMUQZ-SLYNCCJLSA-N ethyl (2r,4r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](C(=O)OC)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UDZDABRIRFMUQZ-SLYNCCJLSA-N 0.000 claims description 2
- VWGMEISAKZYLEN-SVFBPWRDSA-N ethyl (2r,4r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxyethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](COC)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VWGMEISAKZYLEN-SVFBPWRDSA-N 0.000 claims description 2
- XZKOFSOTPUNOAN-WSTZPKSXSA-N ethyl (2r,4r)-4-[(1s)-2-amino-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](CN)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XZKOFSOTPUNOAN-WSTZPKSXSA-N 0.000 claims description 2
- ZBNKVGDBIPQMDG-HBFSDRIKSA-N ethyl (2r,4r)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](C#N)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZBNKVGDBIPQMDG-HBFSDRIKSA-N 0.000 claims description 2
- XVZYJQGDCGJJGF-ZXNZOMRRSA-N ethyl (2r,4r)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-fluoromethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](F)[C@@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XVZYJQGDCGJJGF-ZXNZOMRRSA-N 0.000 claims description 2
- GEENLFPAHWMYKR-POAQFYNOSA-N ethyl (2r,4r)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](O)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GEENLFPAHWMYKR-POAQFYNOSA-N 0.000 claims description 2
- DGJYBTFRHYCBAJ-ZXNZOMRRSA-N ethyl (2r,4r)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](O)[C@@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DGJYBTFRHYCBAJ-ZXNZOMRRSA-N 0.000 claims description 2
- ADFRGNYDGYPUDI-YFVAEKQCSA-N ethyl (2r,4r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-(methylamino)methyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](NC)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ADFRGNYDGYPUDI-YFVAEKQCSA-N 0.000 claims description 2
- ZBNKVGDBIPQMDG-WSTZPKSXSA-N ethyl (2r,4r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](C#N)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZBNKVGDBIPQMDG-WSTZPKSXSA-N 0.000 claims description 2
- XVZYJQGDCGJJGF-LAECCNGNSA-N ethyl (2r,4r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-fluoromethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](F)[C@@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XVZYJQGDCGJJGF-LAECCNGNSA-N 0.000 claims description 2
- GEENLFPAHWMYKR-YVWKXTFCSA-N ethyl (2r,4r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](O)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GEENLFPAHWMYKR-YVWKXTFCSA-N 0.000 claims description 2
- DGJYBTFRHYCBAJ-LAECCNGNSA-N ethyl (2r,4r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](O)[C@@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DGJYBTFRHYCBAJ-LAECCNGNSA-N 0.000 claims description 2
- GVRJPSKQRKUKMO-YFVAEKQCSA-N ethyl (2r,4r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-methoxymethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](OC)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GVRJPSKQRKUKMO-YFVAEKQCSA-N 0.000 claims description 2
- YLKPINRBGQXIBQ-YVWKXTFCSA-N ethyl (2r,4r)-4-[(s)-amino-[3,5-bis(trifluoromethyl)phenyl]methyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](N)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 YLKPINRBGQXIBQ-YVWKXTFCSA-N 0.000 claims description 2
- HSHIMAZYOGBKJU-FHJLPGHOSA-N ethyl (2r,4s)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@](O)(C(=O)OC)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HSHIMAZYOGBKJU-FHJLPGHOSA-N 0.000 claims description 2
- QQCDUYGLFVGVFT-XMYANBKOSA-N ethyl (2r,4s)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxy-2-methoxy-2-oxoethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@](O)(C(=O)OC)[C@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 QQCDUYGLFVGVFT-XMYANBKOSA-N 0.000 claims description 2
- NIKAXGSSAMPHOJ-QWFCFKBJSA-N ethyl (2r,4s)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-fluoroethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](CF)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NIKAXGSSAMPHOJ-QWFCFKBJSA-N 0.000 claims description 2
- UDZDABRIRFMUQZ-YFVAEKQCSA-N ethyl (2r,4s)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](C(=O)OC)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UDZDABRIRFMUQZ-YFVAEKQCSA-N 0.000 claims description 2
- VWGMEISAKZYLEN-SFHLNBCPSA-N ethyl (2r,4s)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxyethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](COC)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VWGMEISAKZYLEN-SFHLNBCPSA-N 0.000 claims description 2
- VRVDKVXKBPPIBG-KCZVDYSFSA-N ethyl (2r,4s)-4-[(1s)-2-acetyloxy-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](COC(C)=O)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VRVDKVXKBPPIBG-KCZVDYSFSA-N 0.000 claims description 2
- XZKOFSOTPUNOAN-QWFCFKBJSA-N ethyl (2r,4s)-4-[(1s)-2-amino-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](CN)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XZKOFSOTPUNOAN-QWFCFKBJSA-N 0.000 claims description 2
- ZBNKVGDBIPQMDG-GGPKGHCWSA-N ethyl (2r,4s)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](C#N)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZBNKVGDBIPQMDG-GGPKGHCWSA-N 0.000 claims description 2
- XVZYJQGDCGJJGF-CNBXIYLPSA-N ethyl (2r,4s)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-fluoromethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](F)[C@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XVZYJQGDCGJJGF-CNBXIYLPSA-N 0.000 claims description 2
- GEENLFPAHWMYKR-KPFFTGBYSA-N ethyl (2r,4s)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](O)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GEENLFPAHWMYKR-KPFFTGBYSA-N 0.000 claims description 2
- DGJYBTFRHYCBAJ-CNBXIYLPSA-N ethyl (2r,4s)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@H](O)[C@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DGJYBTFRHYCBAJ-CNBXIYLPSA-N 0.000 claims description 2
- ZBNKVGDBIPQMDG-QWFCFKBJSA-N ethyl (2r,4s)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](C#N)[C@@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZBNKVGDBIPQMDG-QWFCFKBJSA-N 0.000 claims description 2
- XVZYJQGDCGJJGF-LGZJRCCHSA-N ethyl (2r,4s)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-fluoromethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](F)[C@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XVZYJQGDCGJJGF-LGZJRCCHSA-N 0.000 claims description 2
- GEENLFPAHWMYKR-IMFGXOCKSA-N ethyl (2r,4s)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](O)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GEENLFPAHWMYKR-IMFGXOCKSA-N 0.000 claims description 2
- DGJYBTFRHYCBAJ-LGZJRCCHSA-N ethyl (2r,4s)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-hydroxymethyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](O)[C@H]2C[C@@H](C)N(C3=CC(OC)=C(OC)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DGJYBTFRHYCBAJ-LGZJRCCHSA-N 0.000 claims description 2
- YLKPINRBGQXIBQ-IMFGXOCKSA-N ethyl (2r,4s)-4-[(s)-amino-[3,5-bis(trifluoromethyl)phenyl]methyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1([C@@H](N)[C@H]2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 YLKPINRBGQXIBQ-IMFGXOCKSA-N 0.000 claims description 2
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 230000009103 reabsorption Effects 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 27
- GPTDGDLLZCMCAO-DENIHFKCSA-N ethyl (2r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@H](C(=O)OC)N2C[C@@H](CC)N(C3=CC(C)=C(C)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GPTDGDLLZCMCAO-DENIHFKCSA-N 0.000 claims 1
- GACGKCUQFPNKIC-YLJYHZDGSA-N ethyl (2r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@H](C(=O)OC)N2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GACGKCUQFPNKIC-YLJYHZDGSA-N 0.000 claims 1
- GPTDGDLLZCMCAO-KNQAVFIVSA-N ethyl (2r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@@H](C(=O)OC)N2C[C@@H](CC)N(C3=CC(C)=C(C)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GPTDGDLLZCMCAO-KNQAVFIVSA-N 0.000 claims 1
- GACGKCUQFPNKIC-XLIONFOSSA-N ethyl (2r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6-(trifluoromethyl)-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@@H](C(=O)OC)N2C[C@@H](CC)N(C3=CC=C(C=C32)C(F)(F)F)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GACGKCUQFPNKIC-XLIONFOSSA-N 0.000 claims 1
- HVUDANQHIPTUON-KNQAVFIVSA-N ethyl (2r)-4-[(r)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@H](C#N)N2C[C@@H](CC)N(C3=CC(C)=C(C)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HVUDANQHIPTUON-KNQAVFIVSA-N 0.000 claims 1
- HVUDANQHIPTUON-DENIHFKCSA-N ethyl (2r)-4-[(s)-[3,5-bis(trifluoromethyl)phenyl]-cyanomethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@@H](C#N)N2C[C@@H](CC)N(C3=CC(C)=C(C)C=C32)C(=O)OCC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HVUDANQHIPTUON-DENIHFKCSA-N 0.000 claims 1
- IRSQCHCMPVMXDX-WIYYLYMNSA-N methyl (2r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@H](C(=O)OC)N2C[C@H](N(C3=CC(C)=C(C)C=C32)C(=O)OC)CC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IRSQCHCMPVMXDX-WIYYLYMNSA-N 0.000 claims 1
- IRSQCHCMPVMXDX-NQIIRXRSSA-N methyl (2r)-4-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@@H](C(=O)OC)N2C[C@H](N(C3=CC(C)=C(C)C=C32)C(=O)OC)CC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IRSQCHCMPVMXDX-NQIIRXRSSA-N 0.000 claims 1
- SFKAOCXNTCHYIM-NFBKMPQASA-N propan-2-yl (2r)-4-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-2-oxoethyl]-2-ethyl-6,7-dimethyl-2,3-dihydroquinoxaline-1-carboxylate Chemical compound C1([C@H](C(=O)OC)N2C[C@H](N(C3=CC(C)=C(C)C=C32)C(=O)OC(C)C)CC)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SFKAOCXNTCHYIM-NFBKMPQASA-N 0.000 claims 1
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- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- TVTJZMHAIQQZTL-WATAJHSMSA-M sodium;(2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylate Chemical compound [Na+].C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C([O-])=O)CCCC1=CC=CC=C1 TVTJZMHAIQQZTL-WATAJHSMSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- DZXGOSLAFIELLA-UHFFFAOYSA-N tert-butyl 2-ethyl-4-hydroxy-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound FC(F)(F)C1=CC=C2N(C(=O)OC(C)(C)C)C(CC)CC(O)C2=C1 DZXGOSLAFIELLA-UHFFFAOYSA-N 0.000 description 1
- VHFPXAYACOABRB-UHFFFAOYSA-N tert-butyl 2-ethyl-4-oxo-6-(trifluoromethyl)-2,3-dihydroquinoline-1-carboxylate Chemical compound FC(F)(F)C1=CC=C2N(C(=O)OC(C)(C)C)C(CC)CC(=O)C2=C1 VHFPXAYACOABRB-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
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- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 229950004815 tigestol Drugs 0.000 description 1
- 229940032666 tiludronate disodium Drugs 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical group C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 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
- 229940055755 tricor Drugs 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 108010002139 very low density lipoprotein triglyceride Proteins 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 229940111503 welchol Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229940072252 zestril Drugs 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
- 125000005853 β-dimethylaminoethyl group Chemical group 0.000 description 1
Classifications
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- 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
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- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
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- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US45827403P | 2003-03-28 | 2003-03-28 | |
PCT/IB2004/000836 WO2004085401A1 (en) | 2003-03-28 | 2004-03-15 | 1,2,4-substituted 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydro-quinoxaline derivatives as cetp inhibitors for the treatment of atherosclerosis and obesity |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20050859A2 true HRP20050859A2 (en) | 2006-02-28 |
Family
ID=33098266
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20050859A HRP20050859A2 (en) | 2003-03-28 | 2005-09-28 | 1,2,4-suptituted 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydro-quinoxaline derivatives as cetp inhibitors for the treatment of atherosclerosis and obesity |
Country Status (25)
Country | Link |
---|---|
EP (1) | EP1622872A1 (pt) |
JP (1) | JP2006521344A (pt) |
KR (1) | KR100729883B1 (pt) |
CN (1) | CN1795177A (pt) |
AR (1) | AR044507A1 (pt) |
AU (1) | AU2004224082A1 (pt) |
BR (1) | BRPI0408897A (pt) |
CA (1) | CA2520405A1 (pt) |
CL (1) | CL2004000639A1 (pt) |
EA (1) | EA200501376A1 (pt) |
EC (1) | ECSP056040A (pt) |
GT (1) | GT200400050A (pt) |
HR (1) | HRP20050859A2 (pt) |
MA (1) | MA27828A1 (pt) |
MX (1) | MXPA05010456A (pt) |
NL (1) | NL1025839C2 (pt) |
NO (1) | NO20054989L (pt) |
OA (1) | OA13153A (pt) |
PA (1) | PA8598901A1 (pt) |
PE (1) | PE20050389A1 (pt) |
TN (1) | TNSN05243A1 (pt) |
TW (1) | TWI285641B (pt) |
UY (1) | UY28243A1 (pt) |
WO (1) | WO2004085401A1 (pt) |
ZA (1) | ZA200507819B (pt) |
Families Citing this family (32)
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DK1599468T3 (da) | 2003-01-14 | 2008-02-04 | Arena Pharm Inc | 1,2,3-trisubstituerede aryl- og heteroarylderivater som modulatorer af metabolisme og forebyggelse og behandling af forstyrrelser forbundet dermed såsom diabetes og hyperglykæmi |
US6992096B2 (en) | 2003-04-11 | 2006-01-31 | Ptc Therapeutics, Inc. | 1,2,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease |
EP1644375A2 (en) | 2003-07-14 | 2006-04-12 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
WO2006033001A1 (en) * | 2004-09-23 | 2006-03-30 | Pfizer Products Inc. | Quinoline compounds |
US20070149567A1 (en) * | 2004-09-23 | 2007-06-28 | Pfizer Inc | Quinoline compounds |
AR051780A1 (es) * | 2004-11-29 | 2007-02-07 | Japan Tobacco Inc | Compuestos en anillo fusionados que contienen nitrogeno y utilizacion de los mismos |
MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
AU2006216713A1 (en) * | 2005-02-24 | 2006-08-31 | Millennium Pharmaceuticals, Inc. | PGD2 receptor antagonists for the treatment of inflammatory diseases |
US7888376B2 (en) * | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
PE20071025A1 (es) * | 2006-01-31 | 2007-10-17 | Mitsubishi Tanabe Pharma Corp | Compuesto amina trisustituido |
US7745477B2 (en) * | 2006-02-07 | 2010-06-29 | Hoffman-La Roche Inc. | Heteroaryl and benzyl amide compounds |
UY30244A1 (es) | 2006-03-30 | 2007-11-30 | Tanabe Seiyaku Co | Un proceso para preparar derivados de tetrahidroquinolina |
AU2007247385B2 (en) | 2006-05-10 | 2011-07-14 | Novartis Ag | Bicyclic derivatives as CETP inhibitors |
JP4108729B2 (ja) * | 2006-05-26 | 2008-06-25 | 日本たばこ産業株式会社 | 窒素含有縮合環化合物含有医薬組成物 |
US20080305169A1 (en) * | 2006-05-26 | 2008-12-11 | Japan Tobacco Inc. | Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds |
RU2009122507A (ru) * | 2006-11-15 | 2010-12-20 | Новартис АГ (CH) | Органические соединения |
JP4846769B2 (ja) * | 2007-07-30 | 2011-12-28 | 田辺三菱製薬株式会社 | 医薬組成物 |
CA2696609C (en) | 2007-08-27 | 2017-09-05 | Helicon Therapeutics, Inc. | Therapeutic isoxazole compounds |
WO2010049302A1 (en) * | 2008-10-29 | 2010-05-06 | F. Hoffmann-La Roche Ag | Novel phenyl amide or pyridil amide derivatives and their use as gpbar1 agonists |
US8420647B2 (en) * | 2010-01-21 | 2013-04-16 | Hoffmann-La Roche Inc. | 4-phenoxy-nicotinamide or 4-phenoxy-pyrimidine-5-carboxamide compounds |
EP3323818A1 (en) | 2010-09-22 | 2018-05-23 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
EP3071205B1 (en) * | 2013-11-18 | 2020-02-05 | Forma Therapeutics, Inc. | Benzopiperazine compositions as bet bromodomain inhibitors |
NZ720004A (en) | 2013-11-18 | 2020-03-27 | Forma Therapeutics Inc | Tetrahydroquinoline compositions as bet bromodomain inhibitors |
CN112979575A (zh) | 2014-03-06 | 2021-06-18 | Ptc医疗公司 | 1,2,4-噁二唑苯甲酸的药物组合物和盐 |
EP3242666B1 (en) | 2015-01-06 | 2024-10-16 | Arena Pharmaceuticals, Inc. | Compound for use in treating conditions related to the s1p1 receptor |
PT3310760T (pt) | 2015-06-22 | 2022-11-10 | Arena Pharm Inc | Sal cristalino de l-arginina de ácido (r)-2-(7-(4-ciclopentil-3-(trifluorometil)benziloxi)-1,2,3,4-tetrahidrociclo-penta[b]indol-3-il)acético para utilização em distúrbios associados a recetores de s1p1 |
WO2017075312A1 (en) | 2015-10-30 | 2017-05-04 | Ptc Therapeutics, Inc. | Methods for treating epilepsy |
CA3053418A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
CN110452183B (zh) * | 2019-09-04 | 2023-03-14 | 中国科学院上海有机化学研究所 | 一种手性杂环化合物的制备方法 |
CN111440162A (zh) * | 2020-04-01 | 2020-07-24 | 邱曲真 | 噻唑二氢萘类衍生物及其在代谢性疾病中的应用 |
CN114656406B (zh) * | 2022-01-25 | 2023-09-05 | 阿里生物新材料(常州)有限公司 | 一种2-氟代嘧啶-4-羧酸的合成方法 |
CN115894358A (zh) | 2022-10-25 | 2023-04-04 | 广东省农业科学院蚕业与农产品加工研究所 | 一种具有脂肪酶抑制活性的米糠生物碱、药物组合物及其制备方法和应用 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE351464C (de) * | 1917-12-18 | 1922-04-07 | Chemische Werke Grenzach Aktie | Verfahren zur Darstellung von Derivaten einer hydrierten 2-Phenylchinolin-4-carbonsaeure |
DE69533180T2 (de) * | 1994-12-22 | 2005-07-14 | Ligand Pharmaceuticals, Inc., San Diego | Steroidrezeptor-Modulator Verbindungen und Methoden |
US5965572A (en) * | 1996-10-28 | 1999-10-12 | The United States Of America As Respresented By The Secretary Of The Army | Methods for treating antibiotic-resistant infections |
US6103905A (en) * | 1997-06-19 | 2000-08-15 | Sepracor, Inc. | Quinoline-indole antimicrobial agents, uses and compositions related thereto |
ES2201674T3 (es) * | 1998-01-26 | 2004-03-16 | Smithkline Beecham Plc | Derivados de quinolina con propiedades antibacterianas. |
GT199900147A (es) * | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
CO5271716A1 (es) * | 1999-11-30 | 2003-04-30 | Pfizer Prod Inc | Cristales de 4- carboxamino 1,2,3,4-tetrahidroquinolina 2- sustituida |
-
2004
- 2004-03-15 AU AU2004224082A patent/AU2004224082A1/en not_active Abandoned
- 2004-03-15 WO PCT/IB2004/000836 patent/WO2004085401A1/en active Application Filing
- 2004-03-15 MX MXPA05010456A patent/MXPA05010456A/es unknown
- 2004-03-15 OA OA1200500269A patent/OA13153A/en unknown
- 2004-03-15 CN CNA2004800146455A patent/CN1795177A/zh active Pending
- 2004-03-15 EP EP04720668A patent/EP1622872A1/en not_active Withdrawn
- 2004-03-15 KR KR1020057018383A patent/KR100729883B1/ko not_active IP Right Cessation
- 2004-03-15 EA EA200501376A patent/EA200501376A1/ru unknown
- 2004-03-15 JP JP2006506369A patent/JP2006521344A/ja active Pending
- 2004-03-15 CA CA002520405A patent/CA2520405A1/en not_active Abandoned
- 2004-03-15 BR BRPI0408897-2A patent/BRPI0408897A/pt not_active IP Right Cessation
- 2004-03-23 GT GT200400050A patent/GT200400050A/es unknown
- 2004-03-25 UY UY28243A patent/UY28243A1/es not_active Application Discontinuation
- 2004-03-25 CL CL200400639A patent/CL2004000639A1/es unknown
- 2004-03-26 NL NL1025839A patent/NL1025839C2/nl not_active IP Right Cessation
- 2004-03-26 PE PE2004000323A patent/PE20050389A1/es not_active Application Discontinuation
- 2004-03-26 AR ARP040101024A patent/AR044507A1/es unknown
- 2004-03-26 TW TW093108314A patent/TWI285641B/zh not_active IP Right Cessation
- 2004-03-26 PA PA20048598901A patent/PA8598901A1/es unknown
-
2005
- 2005-09-26 EC EC2005006040A patent/ECSP056040A/es unknown
- 2005-09-27 ZA ZA200507819A patent/ZA200507819B/xx unknown
- 2005-09-28 MA MA28519A patent/MA27828A1/fr unknown
- 2005-09-28 TN TNP2005000243A patent/TNSN05243A1/fr unknown
- 2005-09-28 HR HR20050859A patent/HRP20050859A2/hr not_active Application Discontinuation
- 2005-10-26 NO NO20054989A patent/NO20054989L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
WO2004085401A8 (en) | 2005-12-01 |
KR100729883B1 (ko) | 2007-06-18 |
EA200501376A1 (ru) | 2006-04-28 |
AR044507A1 (es) | 2005-09-14 |
TNSN05243A1 (fr) | 2007-06-11 |
TWI285641B (en) | 2007-08-21 |
PE20050389A1 (es) | 2005-05-30 |
OA13153A (en) | 2006-12-13 |
PA8598901A1 (es) | 2004-11-26 |
UY28243A1 (es) | 2004-11-08 |
NO20054989L (no) | 2005-12-16 |
MXPA05010456A (es) | 2006-03-21 |
NO20054989D0 (no) | 2005-10-26 |
JP2006521344A (ja) | 2006-09-21 |
TW200508222A (en) | 2005-03-01 |
GT200400050A (es) | 2005-03-02 |
MA27828A1 (fr) | 2006-04-03 |
AU2004224082A1 (en) | 2004-10-07 |
CL2004000639A1 (es) | 2005-02-04 |
BRPI0408897A (pt) | 2006-04-18 |
CN1795177A (zh) | 2006-06-28 |
EP1622872A1 (en) | 2006-02-08 |
KR20050115938A (ko) | 2005-12-08 |
CA2520405A1 (en) | 2004-10-07 |
WO2004085401A1 (en) | 2004-10-07 |
ZA200507819B (en) | 2007-04-25 |
ECSP056040A (es) | 2006-01-27 |
NL1025839C2 (nl) | 2006-09-06 |
NL1025839A1 (nl) | 2004-09-30 |
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