JP5819840B2 - ブロモドメイン阻害剤としてのテトラヒドロキノリン誘導体 - Google Patents
ブロモドメイン阻害剤としてのテトラヒドロキノリン誘導体 Download PDFInfo
- Publication number
- JP5819840B2 JP5819840B2 JP2012537383A JP2012537383A JP5819840B2 JP 5819840 B2 JP5819840 B2 JP 5819840B2 JP 2012537383 A JP2012537383 A JP 2012537383A JP 2012537383 A JP2012537383 A JP 2012537383A JP 5819840 B2 JP5819840 B2 JP 5819840B2
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- Japan
- Prior art keywords
- methyl
- acetyl
- tetrahydro
- mmol
- quinolinyl
- Prior art date
- Legal status (The legal status 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 status listed.)
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- 102000001805 Bromodomains Human genes 0.000 title description 23
- 108050009021 Bromodomains Proteins 0.000 title description 21
- 239000003112 inhibitor Substances 0.000 title description 14
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 199
- -1 -CF 3 Chemical group 0.000 claims description 133
- 150000003839 salts Chemical class 0.000 claims description 118
- 229910052757 nitrogen Inorganic materials 0.000 claims description 94
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 235000010233 benzoic acid Nutrition 0.000 claims description 18
- 239000005711 Benzoic acid Substances 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 16
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 16
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 230000001363 autoimmune Effects 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 230000004968 inflammatory condition Effects 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- FAWSUKOIROHXAP-NPMXOYFQSA-N 4-[(2s,4r)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical group N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)C=1C=CC(=CC=1)C(O)=O)C(C)=O)C)C1=CC=C(Cl)C=C1 FAWSUKOIROHXAP-NPMXOYFQSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- PXXDOEMDQBOWHE-UHFFFAOYSA-N 4-[1-acetyl-2-methyl-4-(4-methylanilino)-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(O)=O)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(C)C=C1 PXXDOEMDQBOWHE-UHFFFAOYSA-N 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- VXXFVFXAKOHQIA-IFXJQAMLSA-N 1-[(2s,4r)-4-[(5-fluoropyridin-2-yl)amino]-2-methyl-6-(4-methylimidazol-1-yl)-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)N1C=C(C)N=C1)C(C)=O)C)C1=CC=C(F)C=N1 VXXFVFXAKOHQIA-IFXJQAMLSA-N 0.000 claims description 3
- XBTDPNSDSQVSBA-CCLHPLFOSA-N 1-[(2s,4r)-4-[(5-fluoropyridin-2-yl)amino]-2-methyl-6-[4-(piperidin-1-ylmethyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)C=1C=CC(CN2CCCCC2)=CC=1)C(C)=O)C)C1=CC=C(F)C=N1 XBTDPNSDSQVSBA-CCLHPLFOSA-N 0.000 claims description 3
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- XLHWPLMXJZZFLM-UHFFFAOYSA-N 1-[2-methyl-4-(4-methylanilino)-6-[4-(morpholine-4-carbonyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3C=CC(=CC=3)C(=O)N3CCOCC3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(C)C=C1 XLHWPLMXJZZFLM-UHFFFAOYSA-N 0.000 claims description 2
- LIBBMGDUMSQEGE-UHFFFAOYSA-N 1-[2-methyl-6-[1-[2-(methylamino)ethyl]pyrazol-4-yl]-4-(pyridin-2-ylamino)-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C1=NN(CCNC)C=C1C1=CC=C(N(C(C)CC2NC=3N=CC=CC=3)C(C)=O)C2=C1 LIBBMGDUMSQEGE-UHFFFAOYSA-N 0.000 claims description 2
- YYAUJNXXEJJJEY-UHFFFAOYSA-N 1-[2-methyl-6-[1-[2-(methylamino)ethyl]pyrazol-4-yl]-4-(pyrimidin-2-ylamino)-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C1=NN(CCNC)C=C1C1=CC=C(N(C(C)CC2NC=3N=CC=CN=3)C(C)=O)C2=C1 YYAUJNXXEJJJEY-UHFFFAOYSA-N 0.000 claims description 2
- VLQJGBRQPMWAOG-UHFFFAOYSA-N 1-[4-[(5-fluoropyridin-2-yl)amino]-2-methyl-6-[4-(methylaminomethyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C1=CC(CNC)=CC=C1C1=CC=C(N(C(C)CC2NC=3N=CC(F)=CC=3)C(C)=O)C2=C1 VLQJGBRQPMWAOG-UHFFFAOYSA-N 0.000 claims description 2
- LNIGKABMKQPEJP-UHFFFAOYSA-N 1-[4-anilino-2-methyl-6-[3-(morpholin-4-ylmethyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3C=C(CN4CCOCC4)C=CC=3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=CC=C1 LNIGKABMKQPEJP-UHFFFAOYSA-N 0.000 claims description 2
- HHLPOWRWLBEWKR-UHFFFAOYSA-N 1-[4-anilino-2-methyl-6-[4-(piperidin-1-ylmethyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3C=CC(CN4CCCCC4)=CC=3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=CC=C1 HHLPOWRWLBEWKR-UHFFFAOYSA-N 0.000 claims description 2
- NXGNKWNCNDHXEW-UHFFFAOYSA-N 1-[6-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-4-(pyridin-2-ylamino)-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3N=NN(CCO)C=3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=CC=N1 NXGNKWNCNDHXEW-UHFFFAOYSA-N 0.000 claims description 2
- UQXYDLCFKSSUMO-UHFFFAOYSA-N 1-[6-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-4-[(3-methylpyridin-2-yl)amino]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3N=NN(CCO)C=3)=CC=C2N(C(C)=O)C(C)CC1NC1=NC=CC=C1C UQXYDLCFKSSUMO-UHFFFAOYSA-N 0.000 claims description 2
- HIKJEYPUVIOESF-UHFFFAOYSA-N 1-[6-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-4-[(4-methylpyridin-2-yl)amino]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3N=NN(CCO)C=3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC(C)=CC=N1 HIKJEYPUVIOESF-UHFFFAOYSA-N 0.000 claims description 2
- AGRHDPJTLMEWON-UHFFFAOYSA-N 1-[6-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-4-[(5-methylpyridin-2-yl)amino]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3N=NN(CCO)C=3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(C)C=N1 AGRHDPJTLMEWON-UHFFFAOYSA-N 0.000 claims description 2
- LWAJDCIIKOGJNS-UHFFFAOYSA-N 1-[6-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-4-[(6-methylpyridin-2-yl)amino]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C12=CC(C=3N=NN(CCO)C=3)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=CC(C)=N1 LWAJDCIIKOGJNS-UHFFFAOYSA-N 0.000 claims description 2
- NWUSBAWGHMHOSL-UHFFFAOYSA-N 4-[1-acetyl-2-methyl-4-[(5-methylpyridin-2-yl)amino]-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(O)=O)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(C)C=N1 NWUSBAWGHMHOSL-UHFFFAOYSA-N 0.000 claims description 2
- LCALSMKRLRQSEW-UHFFFAOYSA-N 4-[1-acetyl-2-methyl-4-[3-(trifluoromethyl)anilino]-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(O)=O)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=CC(C(F)(F)F)=C1 LCALSMKRLRQSEW-UHFFFAOYSA-N 0.000 claims description 2
- XPUCQJSAUFPNIJ-UHFFFAOYSA-N 4-[1-acetyl-2-methyl-4-[4-(trifluoromethyl)anilino]-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(O)=O)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(C(F)(F)F)C=C1 XPUCQJSAUFPNIJ-UHFFFAOYSA-N 0.000 claims description 2
- HFOKQPIWNDBDIS-UHFFFAOYSA-N 4-[1-acetyl-4-(4-chloro-n-ethylanilino)-2-methyl-3,4-dihydro-2h-quinolin-6-yl]-n-methylbenzamide Chemical compound C=1C=C(Cl)C=CC=1N(CC)C(C1=C2)CC(C)N(C(C)=O)C1=CC=C2C1=CC=C(C(=O)NC)C=C1 HFOKQPIWNDBDIS-UHFFFAOYSA-N 0.000 claims description 2
- FKMXTZHFWDLVLJ-UHFFFAOYSA-N 4-[1-acetyl-4-(4-cyanoanilino)-2-methyl-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(O)=O)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(C#N)C=C1 FKMXTZHFWDLVLJ-UHFFFAOYSA-N 0.000 claims description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 2
- 229940095102 methyl benzoate Drugs 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- BVXAFKJVGMEQRF-RBISFHTESA-N 1-[(2s,4r)-2-methyl-4-[(5-methylpyridin-2-yl)amino]-6-[4-(piperidin-1-ylmethyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)C=1C=CC(CN2CCCCC2)=CC=1)C(C)=O)C)C1=CC=C(C)C=N1 BVXAFKJVGMEQRF-RBISFHTESA-N 0.000 claims 1
- SAXUXMSUABSPPF-KDYSTLNUSA-N 1-[(2s,4r)-2-methyl-6-[4-(piperidin-1-ylmethyl)phenyl]-4-(pyridin-2-ylamino)-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)C=1C=CC(CN2CCCCC2)=CC=1)C(C)=O)C)C1=CC=CC=N1 SAXUXMSUABSPPF-KDYSTLNUSA-N 0.000 claims 1
- OPPYCJBWBQERQN-CCLHPLFOSA-N 1-[(2s,4r)-4-[(5-chloropyridin-2-yl)amino]-2-methyl-6-[4-(piperidin-1-ylmethyl)phenyl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)C=1C=CC(CN2CCCCC2)=CC=1)C(C)=O)C)C1=CC=C(Cl)C=N1 OPPYCJBWBQERQN-CCLHPLFOSA-N 0.000 claims 1
- ZYWTWMAXCZSRSE-YCRPNKLZSA-N 1-[(2s,4r)-6-(6-aminopyridin-3-yl)-4-anilino-2-methyl-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound N([C@@H]1C[C@@H](N(C2=CC=C(C=C21)C=1C=NC(N)=CC=1)C(C)=O)C)C1=CC=CC=C1 ZYWTWMAXCZSRSE-YCRPNKLZSA-N 0.000 claims 1
- RQAYPLLPEGHEDZ-UHFFFAOYSA-N 1-[4-anilino-2-methyl-6-[1-[2-(methylamino)ethyl]pyrazol-4-yl]-3,4-dihydro-2h-quinolin-1-yl]ethanone Chemical compound C1=NN(CCNC)C=C1C1=CC=C(N(C(C)CC2NC=3C=CC=CC=3)C(C)=O)C2=C1 RQAYPLLPEGHEDZ-UHFFFAOYSA-N 0.000 claims 1
- FAWSUKOIROHXAP-UHFFFAOYSA-N 4-[1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2h-quinolin-6-yl]benzoic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(O)=O)=CC=C2N(C(C)=O)C(C)CC1NC1=CC=C(Cl)C=C1 FAWSUKOIROHXAP-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 582
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 445
- 239000000543 intermediate Substances 0.000 description 255
- 239000000203 mixture Substances 0.000 description 252
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 214
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 162
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 157
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 146
- 238000000034 method Methods 0.000 description 137
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 130
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 124
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 123
- 238000002360 preparation method Methods 0.000 description 118
- 230000014759 maintenance of location Effects 0.000 description 112
- 235000002639 sodium chloride Nutrition 0.000 description 106
- 239000007787 solid Substances 0.000 description 98
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 97
- 239000000243 solution Substances 0.000 description 97
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 94
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 83
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 74
- 239000012074 organic phase Substances 0.000 description 70
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 69
- 239000010410 layer Substances 0.000 description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 57
- 239000000377 silicon dioxide Substances 0.000 description 55
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 30
- 239000003607 modifier Substances 0.000 description 29
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- 239000000706 filtrate Substances 0.000 description 28
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 22
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- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 20
- 238000001819 mass spectrum Methods 0.000 description 20
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Classifications
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- 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
- C07D401/12—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 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
- C07D409/10—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 aromatic rings
-
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Immunology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB0919434.1A GB0919434D0 (en) | 2009-11-05 | 2009-11-05 | Novel compounds |
| GB0919434.1 | 2009-11-05 | ||
| PCT/EP2010/066701 WO2011054848A1 (en) | 2009-11-05 | 2010-11-03 | Thetrahydroquinolines derivatives as bromodomain inhibitors |
Publications (3)
| Publication Number | Publication Date |
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| JP2013510125A JP2013510125A (ja) | 2013-03-21 |
| JP2013510125A5 JP2013510125A5 (enExample) | 2013-11-14 |
| JP5819840B2 true JP5819840B2 (ja) | 2015-11-24 |
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| US (1) | US8580957B2 (enExample) |
| EP (1) | EP2496558B1 (enExample) |
| JP (1) | JP5819840B2 (enExample) |
| ES (1) | ES2573706T3 (enExample) |
| GB (1) | GB0919434D0 (enExample) |
| WO (1) | WO2011054848A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014511892A (ja) * | 2011-04-21 | 2014-05-19 | グラクソスミスクライン エルエルシー | ブロモドメイン阻害剤として有用なテトラヒドロキノリン誘導体 |
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| GB0919431D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
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| US9301962B2 (en) | 2010-05-14 | 2016-04-05 | Baylor College Of Medicine | Male contraceptive compositions and methods of use |
| MX384074B (es) | 2010-05-14 | 2025-03-12 | Dana Farber Cancer Inst Inc | Composiciones y métodos para tratar neoplasias, enfermedades inflamatorias y otros trastornos. |
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| GB201107325D0 (en) * | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
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| GB201114103D0 (en) * | 2011-08-17 | 2011-09-28 | Glaxosmithkline Llc | Novel compounds |
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| GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| SE0101161D0 (sv) * | 2001-03-30 | 2001-03-30 | Astrazeneca Ab | New compounds |
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| EP1435356A1 (en) * | 2003-01-06 | 2004-07-07 | Warner-Lambert Company LLC | Quinoline derivatives as CRTH2 antagonists |
| CN1901958B (zh) | 2003-11-03 | 2011-03-09 | 葛兰素集团有限公司 | 流体分配装置 |
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| WO2007084625A2 (en) * | 2006-01-19 | 2007-07-26 | Mount Sinai School Of Medicine | Novel compounds and methods for inhibiting p53 activity |
| JP2008156311A (ja) | 2006-12-26 | 2008-07-10 | Institute Of Physical & Chemical Research | Ｂｒｄ２ブロモドメイン結合剤 |
| JP5466507B2 (ja) | 2007-09-27 | 2014-04-09 | 興和株式会社 | テトラヒドロキノリン化合物を有効成分とする貧血の予防及び／又は治療剤 |
| US8476260B2 (en) | 2007-12-28 | 2013-07-02 | Mitsubishi Tanabe Pharma Corporation | Antitumor agent |
| EP2415764A4 (en) | 2009-03-31 | 2012-08-08 | Kowa Co | PROPHYLACTIC AND / OR THERAPEUTIC AGENT AGAINST ANEMIA WITH A TETRAHYDROCHINOLINE COMPOUND AS AN ACTIVE SUBSTANCE |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014511892A (ja) * | 2011-04-21 | 2014-05-19 | グラクソスミスクライン エルエルシー | ブロモドメイン阻害剤として有用なテトラヒドロキノリン誘導体 |
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| EP2496558A1 (en) | 2012-09-12 |
| GB0919434D0 (en) | 2009-12-23 |
| US20120208814A1 (en) | 2012-08-16 |
| WO2011054848A1 (en) | 2011-05-12 |
| ES2573706T3 (es) | 2016-06-09 |
| US8580957B2 (en) | 2013-11-12 |
| EP2496558B1 (en) | 2016-03-30 |
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