NO327098B1 - 4-oksokinolin forbindelser, anvendelser derav, farmasoytiske sammensetninger samt kommersielle forpakninger - Google Patents
4-oksokinolin forbindelser, anvendelser derav, farmasoytiske sammensetninger samt kommersielle forpakninger Download PDFInfo
- Publication number
- NO327098B1 NO327098B1 NO20043004A NO20043004A NO327098B1 NO 327098 B1 NO327098 B1 NO 327098B1 NO 20043004 A NO20043004 A NO 20043004A NO 20043004 A NO20043004 A NO 20043004A NO 327098 B1 NO327098 B1 NO 327098B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- oxo
- dihydroquinoline
- carboxylic acid
- chloro
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical class C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 title description 3
- 238000004806 packaging method and process Methods 0.000 title description 2
- -1 4-oxoquinoline compound Chemical class 0.000 claims description 601
- 239000000203 mixture Substances 0.000 claims description 263
- 150000001875 compounds Chemical class 0.000 claims description 188
- 125000005843 halogen group Chemical group 0.000 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 116
- 125000001424 substituent group Chemical group 0.000 claims description 100
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 94
- 150000003839 salts Chemical class 0.000 claims description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 108010061833 Integrases Proteins 0.000 claims description 29
- 238000004519 manufacturing process Methods 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 claims description 21
- 229940124411 anti-hiv antiviral agent Drugs 0.000 claims description 21
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 12
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
- 230000036436 anti-hiv Effects 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 230000000840 anti-viral effect Effects 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 239000003443 antiviral agent Substances 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 229940124524 integrase inhibitor Drugs 0.000 claims description 6
- 239000002850 integrase inhibitor Substances 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- JZCZZGZHZXJOHY-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl JZCZZGZHZXJOHY-UHFFFAOYSA-N 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 claims description 4
- QYFLJDZFSUYSQK-UHFFFAOYSA-N 6-[(3-chloro-2-fluorophenyl)methyl]-1-(2-hydroxyethyl)-7-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=CC=2N(CCO)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1F QYFLJDZFSUYSQK-UHFFFAOYSA-N 0.000 claims description 4
- FGDKSWTXAWITSZ-LJQANCHMSA-N 6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N([C@H](CO)C(C)(C)C)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1F FGDKSWTXAWITSZ-LJQANCHMSA-N 0.000 claims description 4
- 208000037357 HIV infectious disease Diseases 0.000 claims description 4
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 claims description 4
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 claims description 4
- 101100326677 Onchocerca volvulus crt-1 gene Proteins 0.000 claims description 4
- 230000003612 virological effect Effects 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 claims description 3
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 claims description 3
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 claims description 3
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 claims description 3
- KCYXSYRXHHMSBC-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-8-fluoro-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C(F)=C2N(CCO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl KCYXSYRXHHMSBC-UHFFFAOYSA-N 0.000 claims description 3
- QAWVGLOXVAPGQF-UHFFFAOYSA-N 6-[(2-chloro-5-methylphenyl)methyl]-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=CC=C(Cl)C(CC=2C=C3C(=O)C(C(O)=O)=CN(CCO)C3=CC=2)=C1 QAWVGLOXVAPGQF-UHFFFAOYSA-N 0.000 claims description 3
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 claims description 3
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 claims description 3
- SFMJNHNUOVADRW-UHFFFAOYSA-N n-[5-[9-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,6]naphthyridin-1-yl]-2-methylphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(C)=CC=C1N1C(=O)C=CC2=C1C1=CC(C=3C=CC(NS(C)(=O)=O)=CC=3)=CC=C1N=C2 SFMJNHNUOVADRW-UHFFFAOYSA-N 0.000 claims description 3
- UDKLDLMPRXYJPF-UHFFFAOYSA-N 1-(2-amino-2-oxoethyl)-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CC(=O)N)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl UDKLDLMPRXYJPF-UHFFFAOYSA-N 0.000 claims description 2
- DWJZYCRBKJQBIA-UHFFFAOYSA-N 1-(2-aminoethyl)-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCN)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl DWJZYCRBKJQBIA-UHFFFAOYSA-N 0.000 claims description 2
- YUKIZQHXWJBIDQ-UHFFFAOYSA-N 1-(2-carboxyethyl)-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCC(=O)O)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl YUKIZQHXWJBIDQ-UHFFFAOYSA-N 0.000 claims description 2
- UEWUZJWIHIZVTK-UHFFFAOYSA-N 1-(2-hydroxyethyl)-4-oxo-6-[(2-phenylphenyl)methyl]quinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC=C1C1=CC=CC=C1 UEWUZJWIHIZVTK-UHFFFAOYSA-N 0.000 claims description 2
- VYUJPIITHOYCTR-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-(naphthalen-1-ylmethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(CC=3C=C4C(=O)C(C(O)=O)=CN(C4=CC=3)CCO)=CC=CC2=C1 VYUJPIITHOYCTR-UHFFFAOYSA-N 0.000 claims description 2
- CFEGNHQJIFSPIA-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-[(2-hydroxyphenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC=C1O CFEGNHQJIFSPIA-UHFFFAOYSA-N 0.000 claims description 2
- RLHAQLUPZRYYSY-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-[(2-methylsulfonylphenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1CC1=CC=C(N(CCO)C=C(C(O)=O)C2=O)C2=C1 RLHAQLUPZRYYSY-UHFFFAOYSA-N 0.000 claims description 2
- MWUKLMZOJMKFOF-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-[[2-[methyl(methylsulfonyl)amino]phenyl]methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound CS(=O)(=O)N(C)C1=CC=CC=C1CC1=CC=C(N(CCO)C=C(C(O)=O)C2=O)C2=C1 MWUKLMZOJMKFOF-UHFFFAOYSA-N 0.000 claims description 2
- FAKYGLCBFPPNLA-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-[[2-[methyl(propan-2-yl)amino]phenyl]methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound CC(C)N(C)C1=CC=CC=C1CC1=CC=C(N(CCO)C=C(C(O)=O)C2=O)C2=C1 FAKYGLCBFPPNLA-UHFFFAOYSA-N 0.000 claims description 2
- PDHOMFSZQFEZBI-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-[[2-[methyl(propyl)amino]phenyl]methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound CCCN(C)C1=CC=CC=C1CC1=CC=C(N(CCO)C=C(C(O)=O)C2=O)C2=C1 PDHOMFSZQFEZBI-UHFFFAOYSA-N 0.000 claims description 2
- NLLFGVOXJVFWDR-UHFFFAOYSA-N 1-(3-amino-3-oxopropyl)-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCC(=O)N)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl NLLFGVOXJVFWDR-UHFFFAOYSA-N 0.000 claims description 2
- CGRYPFQLSPYBQD-UHFFFAOYSA-N 1-(carboxymethyl)-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CC(=O)O)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl CGRYPFQLSPYBQD-UHFFFAOYSA-N 0.000 claims description 2
- WHQBNOZWJLRENH-UHFFFAOYSA-N 1-acetamido-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(NC(=O)C)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl WHQBNOZWJLRENH-UHFFFAOYSA-N 0.000 claims description 2
- JQPWHLNLPBVDKY-UHFFFAOYSA-N 1-butyl-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCCC)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl JQPWHLNLPBVDKY-UHFFFAOYSA-N 0.000 claims description 2
- JXKPFBAJPSOGAY-UHFFFAOYSA-N 1-cyclobutyl-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC=C(CC=3C(=C(Cl)C=CC=3)Cl)C=C2C(=O)C(C(=O)O)=CN1C1CCC1 JXKPFBAJPSOGAY-UHFFFAOYSA-N 0.000 claims description 2
- GFCMHRKZGQNTIO-UHFFFAOYSA-N 1-cyclopentyl-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC=C(CC=3C(=C(Cl)C=CC=3)Cl)C=C2C(=O)C(C(=O)O)=CN1C1CCCC1 GFCMHRKZGQNTIO-UHFFFAOYSA-N 0.000 claims description 2
- ZKONNXPBZRRVQB-UHFFFAOYSA-N 1-cyclopropyl-6-[(2,3-dichlorophenyl)methyl]-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC=C(CC=3C(=C(Cl)C=CC=3)Cl)C=C2C(=O)C(C(=O)O)=CN1C1CC1 ZKONNXPBZRRVQB-UHFFFAOYSA-N 0.000 claims description 2
- ILNJBIQQAIIMEY-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CN=C21 ILNJBIQQAIIMEY-UHFFFAOYSA-N 0.000 claims description 2
- DSLFTSDXEBBRHC-UHFFFAOYSA-N 5-cyano-6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CCO)C=C(C(O)=O)C(=O)C2=C(C#N)C=1CC1=CC=CC(Cl)=C1Cl DSLFTSDXEBBRHC-UHFFFAOYSA-N 0.000 claims description 2
- KJZKPRJIGJEYTP-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(1,3-dihydroxypropan-2-yl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(C(CO)CO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl KJZKPRJIGJEYTP-UHFFFAOYSA-N 0.000 claims description 2
- IKZKBOGLKXVNPW-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2,3-dihydroxypropyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CC(O)CO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl IKZKBOGLKXVNPW-UHFFFAOYSA-N 0.000 claims description 2
- IEGGLJOZXUZXQR-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-fluoroethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C2C(=O)C(C(=O)O)=CN(CCF)C2=CC=C1CC1=CC=CC(Cl)=C1Cl IEGGLJOZXUZXQR-UHFFFAOYSA-N 0.000 claims description 2
- DATNRCFRYYMMLG-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxy-2-methylpropyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CC(C)(O)C)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl DATNRCFRYYMMLG-UHFFFAOYSA-N 0.000 claims description 2
- SPVHVBZGDZDCJS-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxy-2-phenylethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=CC=CC=1C(O)CN(C1=CC=2)C=C(C(O)=O)C(=O)C1=CC=2CC1=CC=CC(Cl)=C1Cl SPVHVBZGDZDCJS-UHFFFAOYSA-N 0.000 claims description 2
- DNZIJGPLYCYKQP-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxo-7-(trifluoromethyl)quinoline-3-carboxylic acid Chemical compound FC(F)(F)C=1C=C2N(CCO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl DNZIJGPLYCYKQP-UHFFFAOYSA-N 0.000 claims description 2
- FOBWFGSFHDPTIR-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxoquinoline-3,7-dicarboxylic acid Chemical compound OC(=O)C=1C=C2N(CCO)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl FOBWFGSFHDPTIR-UHFFFAOYSA-N 0.000 claims description 2
- OFQROYGZKJFJEC-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-5-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=CC=2N(CCO)C=C(C(O)=O)C(=O)C=2C(OC)=C1CC1=CC=CC(Cl)=C1Cl OFQROYGZKJFJEC-UHFFFAOYSA-N 0.000 claims description 2
- ZXDMPBVTUADOPS-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-7-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=CC=2N(CCO)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1Cl ZXDMPBVTUADOPS-UHFFFAOYSA-N 0.000 claims description 2
- WBSJEVXLQLNTQL-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-7-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=CC=2N(CCO)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1Cl WBSJEVXLQLNTQL-UHFFFAOYSA-N 0.000 claims description 2
- GPNLOOCOILDAHX-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C(C(C(C(O)=O)=CN2CCO)=O)=C2C(OC)=CC=1CC1=CC=CC(Cl)=C1Cl GPNLOOCOILDAHX-UHFFFAOYSA-N 0.000 claims description 2
- QXOXVPGNNUUUKT-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxypropyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C=1C=C2N(CC(O)C)C=C(C(O)=O)C(=O)C2=CC=1CC1=CC=CC(Cl)=C1Cl QXOXVPGNNUUUKT-UHFFFAOYSA-N 0.000 claims description 2
- CQEQLHDOLABNJW-UHFFFAOYSA-N 6-[(2,3-dichlorophenyl)methyl]-1-(2-imidazol-1-ylethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC=C(CC=3C(=C(Cl)C=CC=3)Cl)C=C2C(=O)C(C(=O)O)=CN1CCN1C=CN=C1 CQEQLHDOLABNJW-UHFFFAOYSA-N 0.000 claims description 2
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- BEUUJDAEPJZWHM-COROXYKFSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(2-methoxyethylamino)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[(2,3,4-trimethoxyphenyl)methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@H](C(=O)NCCOC)C(C)C)CC=1C(=C(OC)C(OC)=CC=1)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 BEUUJDAEPJZWHM-COROXYKFSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
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JP2002336843 | 2002-11-20 | ||
JP2003065807 | 2003-03-11 | ||
JP2003139616 | 2003-05-16 | ||
PCT/JP2003/014773 WO2004046115A1 (ja) | 2002-11-20 | 2003-11-20 | 4−オキソキノリン化合物及びそのhivインテグラーゼ阻害剤としての利用 |
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NO20043004L NO20043004L (no) | 2004-07-14 |
NO327098B1 true NO327098B1 (no) | 2009-04-20 |
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NO2013015C NO2013015I2 (no) | 2002-11-20 | 2013-11-07 | Elvitegravir i alle former beskyttet ved basispatentet |
NO2022032C NO2022032I1 (no) | 2002-11-20 | 2022-07-22 | Elvitegravir or a pharmaceutically acceptable salt thereof - Forlenget SPC |
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NO2013015C NO2013015I2 (no) | 2002-11-20 | 2013-11-07 | Elvitegravir i alle former beskyttet ved basispatentet |
NO2022032C NO2022032I1 (no) | 2002-11-20 | 2022-07-22 | Elvitegravir or a pharmaceutically acceptable salt thereof - Forlenget SPC |
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EP (5) | EP3406596A1 (sk) |
KR (1) | KR100665919B1 (sk) |
AR (2) | AR042095A1 (sk) |
AT (1) | ATE443048T1 (sk) |
AU (1) | AU2003302029B8 (sk) |
BE (1) | BE2013C063I2 (sk) |
BR (1) | BRPI0306214B1 (sk) |
CA (1) | CA2470365C (sk) |
CY (2) | CY1110690T1 (sk) |
CZ (1) | CZ2004764A3 (sk) |
DE (1) | DE60329318D1 (sk) |
DK (1) | DK1564210T5 (sk) |
ES (1) | ES2329240T3 (sk) |
FR (1) | FR13C0061I2 (sk) |
HK (1) | HK1080852A1 (sk) |
HU (1) | HUS1300066I1 (sk) |
IL (2) | IL162548A0 (sk) |
LT (1) | LTPA2013018I1 (sk) |
LU (1) | LU92307I2 (sk) |
MX (1) | MXPA04006553A (sk) |
MY (1) | MY136173A (sk) |
NO (3) | NO327098B1 (sk) |
NZ (1) | NZ533641A (sk) |
PE (1) | PE20040840A1 (sk) |
PT (1) | PT1564210E (sk) |
SI (1) | SI1564210T1 (sk) |
SK (1) | SK2662004A3 (sk) |
TR (1) | TR200401663T1 (sk) |
TW (1) | TWI248928B (sk) |
WO (1) | WO2004046115A1 (sk) |
ZA (1) | ZA200404537B (sk) |
Families Citing this family (80)
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SI1441735T1 (sl) | 2001-10-26 | 2006-06-30 | Angeletti P Ist Richerche Bio | N-substituirani hidroksipirimidinon-karboksamidniinhibitorji HIV-integraze |
EP3406596A1 (en) * | 2002-11-20 | 2018-11-28 | Japan Tobacco Inc. | 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
DE602005023717D1 (de) * | 2004-03-10 | 2010-11-04 | Usa | Chinolin-4-one als inhibitoren der retroviralen integrase zur behandlung von hiv, aids und aids-related complex (arc) |
MY134672A (en) * | 2004-05-20 | 2007-12-31 | Japan Tobacco Inc | Stable crystal of 4-oxoquinoline compound |
US7531554B2 (en) | 2004-05-20 | 2009-05-12 | Japan Tobacco Inc. | 4-oxoquinoline compound and use thereof as HIV integrase inhibitor |
US8633219B2 (en) * | 2004-05-21 | 2014-01-21 | Japan Tobacco Inc. | Combination therapy |
WO2006033422A1 (ja) * | 2004-09-21 | 2006-03-30 | Japan Tobacco Inc. | キノリジノン化合物、およびそのhivインテグラーゼ阻害剤としての利用 |
US7745459B2 (en) | 2004-09-21 | 2010-06-29 | Japan Tobacco Inc. | Quinolizinone compound and use thereof as HIV integrase inhibitor |
UA87884C2 (uk) * | 2004-12-03 | 2009-08-25 | Мерк Энд Ко., Инк. | Безводна кристалічна калієва сіль інгібітора віл-інтегрази |
US7772191B2 (en) | 2005-05-10 | 2010-08-10 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein |
US20070032522A1 (en) * | 2005-07-01 | 2007-02-08 | Kumar Dange V | Antiviral agents |
WO2007063869A1 (ja) * | 2005-11-30 | 2007-06-07 | Japan Tobacco Inc. | 高純度キノロン化合物の製造方法 |
SG170796A1 (en) * | 2005-12-30 | 2011-05-30 | Gilead Sciences Inc Us | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
US20090233964A1 (en) * | 2005-12-30 | 2009-09-17 | Gilead Sciences, Inc. | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
AU2013203476C1 (en) * | 2005-12-30 | 2016-11-17 | Gilead Sciences, Inc. | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
US20090018162A1 (en) * | 2006-02-01 | 2009-01-15 | Yuji Matsuzaki | Use of 6-(3-chloro-2-fluorobenzyl)-1-[(2s)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or salt thereof for treating retrovirus infection |
WO2007092802A1 (en) * | 2006-02-09 | 2007-08-16 | Boehringer Ingelheim International Gmbh | Method for treating hiv infection through co-administration of tipranavir and gs 9137 |
WO2007102499A1 (ja) * | 2006-03-06 | 2007-09-13 | Japan Tobacco Inc. | 4-オキソキノリン化合物の製造方法 |
CA2645119C (en) | 2006-03-06 | 2012-01-24 | Japan Tobacco Inc. | Method for producing 4-oxoquinoline compound |
PE20080697A1 (es) | 2006-05-03 | 2008-08-05 | Boehringer Ingelheim Int | Derivados de benzonitrilo sustituidos con glucopiranosilo, composiciones farmaceuticas que contienen compuestos de este tipo, su uso y procedimiento para su fabricacion |
TW200811153A (en) * | 2006-06-23 | 2008-03-01 | Japan Tobacco Inc | 6-(heterocyclyl-substituted benzyl)-4-oxoquinoline compound and use thereof as HIV integrase inhibitor |
KR101636221B1 (ko) | 2006-07-07 | 2016-07-04 | 길리애드 사이언시즈, 인코포레이티드 | 치료제의 약동학 특성의 모듈레이터 |
CA2657034A1 (en) * | 2006-07-19 | 2008-01-24 | University Of Georgia Research Foundation, Inc. | Pyridinone diketo acids: inhibitors of hiv replication in combination therapy |
JP5221544B2 (ja) * | 2006-09-12 | 2013-06-26 | ギリアード サイエンシーズ, インコーポレイテッド | インテグラーゼ阻害剤を調製するためのプロセスおよび中間体 |
EA016267B1 (ru) | 2006-09-29 | 2012-03-30 | Айденикс Фармасьютикалз, Инк. | Энантиомерно чистые фосфоиндолы в качестве ингибиторов hiv |
EP2269992A1 (en) | 2006-12-22 | 2011-01-05 | Avexa Limited | Bicyclic pyrimidinones for the treatment of viral infections |
LT2487162T (lt) * | 2007-02-23 | 2016-11-10 | Gilead Sciences, Inc. | Terapinių agentų farmakokinetinių savybių moduliatoriai |
BRPI0813000A2 (pt) * | 2007-06-29 | 2014-12-23 | Gilead Sciences Inc | Composições terapêuticas e uso das mesmas |
AP2490A (en) * | 2007-06-29 | 2012-10-04 | Gilead Sciences Inc | Therapeutic compositions and the use thereof |
PE20090938A1 (es) | 2007-08-16 | 2009-08-08 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un derivado de benceno sustituido con glucopiranosilo |
AR068403A1 (es) * | 2007-09-11 | 2009-11-18 | Gilead Sciences Inc | Proceso e intermediarios para la preparacion de inhibidores de integrasa |
EP2197847B1 (en) * | 2007-09-12 | 2012-11-07 | Concert Pharmaceuticals Inc. | Deuterated 4 -oxoquinoline derivative for the treatment of hiv infection |
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