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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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
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- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Quinoline Compounds (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)
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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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| 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 |
Families Citing this family (110)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0919431D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| EP2902030B1 (en) | 2010-05-14 | 2016-09-14 | Dana-Farber Cancer Institute, Inc. | Thienotriazolodiazepine compounds for treating neoplasia |
| WO2011143660A2 (en) | 2010-05-14 | 2011-11-17 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating leukemia |
| CN103180318B (zh) | 2010-05-14 | 2017-05-10 | 达那-法伯癌症研究所 | 雄性避孕组合物以及使用方法 |
| AR084070A1 (es) | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| US9249161B2 (en) | 2010-12-02 | 2016-02-02 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| GB201106743D0 (en) | 2011-04-21 | 2011-06-01 | Glaxosmithkline Llc | Novel compounds |
| GB201107325D0 (en) * | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
| WO2012151512A2 (en) | 2011-05-04 | 2012-11-08 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| WO2012174487A2 (en) | 2011-06-17 | 2012-12-20 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| GB201114103D0 (en) * | 2011-08-17 | 2011-09-28 | Glaxosmithkline Llc | Novel compounds |
| WO2013027168A1 (en) | 2011-08-22 | 2013-02-28 | Pfizer Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| WO2013033269A1 (en) * | 2011-08-29 | 2013-03-07 | Coferon, Inc. | Bioorthogonal monomers capable of dimerizing and targeting bromodomains and methods of using same |
| WO2013097052A1 (en) * | 2011-12-30 | 2013-07-04 | Abbott Laboratories | Bromodomain inhibitors |
| CA2870931A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Isoindolone derivatives |
| WO2013184878A1 (en) | 2012-06-06 | 2013-12-12 | Constellation Pharmaceuticals, Inc. | Benzo [b] isoxazoloazepine bromodomain inhibitors and uses thereof |
| TWI602820B (zh) | 2012-06-06 | 2017-10-21 | 星宿藥物公司 | 溴域抑制劑及其用途 |
| EP2858982A4 (en) | 2012-06-12 | 2015-11-11 | Abbvie Inc | PYRIDINONE AND PYRIDAZINONE DERIVATIVES |
| WO2013192274A2 (en) | 2012-06-19 | 2013-12-27 | The Broad Institute, Inc. | Diagnostic and treatment methods in subjects having or at risk of developing resistance to cancer therapy |
| MX2015007921A (es) | 2012-12-21 | 2016-03-03 | Zenith Epigenetics Corp | Compuestos heterociclicos novedosos como inhibidores de bromodominio. |
| CN105377851B (zh) | 2013-03-11 | 2018-07-20 | 密执安州立大学董事会 | Bet布罗莫结构域抑制剂和使用这些抑制剂的治疗方法 |
| EP2968360B1 (en) * | 2013-03-14 | 2021-01-20 | ConverGene LLC | Quinolinone derivatives for the inhibition of bromodomain-containing proteins |
| WO2014140077A1 (en) | 2013-03-14 | 2014-09-18 | Glaxosmithkline Intellectual Property (No.2) Limited | Furopyridines as bromodomain inhibitors |
| WO2014159392A1 (en) | 2013-03-14 | 2014-10-02 | Dana-Farber Cancer Institute, Inc. | Bromodomain binding reagents and uses thereof |
| ES2704048T3 (es) * | 2013-03-14 | 2019-03-14 | Glaxosmithkline Ip No 2 Ltd | Derivados de 1-acil-4-amino-1,2,3,4-tetrahidroquinolina-2,3-disustituida y su uso como inhibidores de bromodominio |
| MX366703B (es) | 2013-03-15 | 2019-07-22 | Incyte Holdings Corp | Heterociclos tricíclicos como inhibidores de la proteína bet. |
| CA2901083A1 (en) | 2013-04-26 | 2014-10-30 | Beigene, Ltd. | Substituted 5-(3,5-dimethylisoxazol-4-yl)indoline-2-ones |
| WO2015004534A2 (en) | 2013-06-21 | 2015-01-15 | Zenith Epigenetics Corp. | Novel substituted bicyclic compounds as bromodomain inhibitors |
| CN105407888B (zh) * | 2013-06-21 | 2019-05-21 | 齐尼思表观遗传学有限公司 | 新双环溴结构域抑制剂 |
| AR096758A1 (es) * | 2013-06-28 | 2016-02-03 | Abbvie Inc | Inhibidores cristalinos de bromodominios |
| MX2015017963A (es) | 2013-06-28 | 2016-11-10 | Abbvie Inc | Inhibidores de bromodominio. |
| WO2015006193A1 (en) | 2013-07-08 | 2015-01-15 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| CA2918910A1 (en) | 2013-07-25 | 2015-01-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of transcription factors and uses thereof |
| JP6542212B2 (ja) | 2013-07-31 | 2019-07-10 | ゼニス・エピジェネティクス・リミテッドＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｌｔｄ． | ブロモドメイン阻害剤としての新規キナゾリノン |
| EA035727B1 (ru) * | 2013-10-18 | 2020-07-31 | Селджен Квонтисел Рисёрч, Инк. | Ингибиторы бромодомена |
| EP3066101B1 (en) | 2013-11-08 | 2020-07-29 | Dana-Farber Cancer Institute, Inc. | Combination therapy for cancer using bromodomain and extra-terminal (bet) protein inhibitors |
| WO2015074081A1 (en) | 2013-11-18 | 2015-05-21 | Bair Kenneth W | Benzopiperazine compositions as bet bromodomain inhibitors |
| BR112016011024B1 (pt) * | 2013-11-18 | 2020-09-01 | Forma Therapeutics, Inc | Composto, composição farmacêutica, e, usos dos mesmos |
| WO2015081189A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
| US9108953B2 (en) * | 2013-11-26 | 2015-08-18 | Gilead Sciences, Inc. | Quinoline derivatives as bromodomain inhibitors |
| US9399640B2 (en) | 2013-11-26 | 2016-07-26 | Incyte Corporation | Substituted pyrrolo[2,3-c]pyridines and pyrazolo[3,4-c]pyridines as BET protein inhibitors |
| US9309246B2 (en) | 2013-12-19 | 2016-04-12 | Incyte Corporation | Tricyclic heterocycles as BET protein inhibitors |
| LT3092227T (lt) * | 2014-01-09 | 2018-08-10 | Orion Corporation | Bicikliniai heterocikliniai dariniai kaip bromodomeno inhibitoriai |
| EA038715B1 (ru) * | 2014-01-24 | 2021-10-08 | Селджен Квонтисел Рисёрч, Инк. | Ингибиторы бромодомена |
| KR20160115953A (ko) | 2014-01-31 | 2016-10-06 | 다나-파버 캔서 인스티튜트 인크. | 디아미노피리미딘 벤젠술폰 유도체 및 그의 용도 |
| JP2017504651A (ja) | 2014-01-31 | 2017-02-09 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | ジアゼパン誘導体の使用 |
| JP2017504650A (ja) | 2014-01-31 | 2017-02-09 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | ジアゼパン誘導体およびその使用 |
| WO2015131005A1 (en) | 2014-02-28 | 2015-09-03 | The Regents Of The University Of Michigan | 9h-pyrimido[4,5-b]indoles and related analogs as bet bromodomain inhibitors |
| CN106456653A (zh) | 2014-02-28 | 2017-02-22 | 腾沙治疗公司 | 高胰岛素血症相关病症的治疗 |
| SI3674302T1 (sl) | 2014-04-23 | 2023-07-31 | Incyte Holdings Corporation | 1h-pirolo(2,3-c)piridin-7(6h)-oni in pirazolo(3,4-c)piridin-7(6h)-oni kot zaviralci proteinov bet |
| PT3157928T (pt) | 2014-06-20 | 2019-05-30 | Constellation Pharmaceuticals Inc | Formas cristalinas de 2-((4s)-6-(4-clorofenil)-1-metil-4h-benzo[c] isoxazolo[4,5-e]azepin-4-il)acetamida |
| JP2017526741A (ja) | 2014-08-08 | 2017-09-14 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | ジアゼパン誘導体およびその使用 |
| CN106793775B (zh) | 2014-08-08 | 2020-06-02 | 达纳-法伯癌症研究所股份有限公司 | 二氢碟啶酮衍生物及其用途 |
| ES2705623T3 (es) * | 2014-09-12 | 2019-03-26 | Glaxosmithkline Ip No 2 Ltd | Derivados de tetrahidroquinolina como inhibidores del bromodominio |
| ES2855225T3 (es) | 2014-09-15 | 2021-09-23 | Incyte Corp | Heterociclos tricíclicos para su uso como inhibidores de proteínas BET |
| SG11201703414VA (en) | 2014-10-27 | 2017-05-30 | Tensha Therapeutics Inc | Bromodomain inhibitors |
| CA2966303A1 (en) | 2014-12-01 | 2016-06-09 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
| CA2966298A1 (en) | 2014-12-01 | 2016-06-09 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| WO2016092375A1 (en) | 2014-12-11 | 2016-06-16 | Zenith Epigenetics Corp. | Substituted heterocycles as bromodomain inhibitors |
| CN107406438B (zh) | 2014-12-17 | 2021-05-14 | 恒翼生物医药科技(上海)有限公司 | 溴结构域的抑制剂 |
| EP3262045A1 (en) | 2015-02-27 | 2018-01-03 | The Regents of The University of Michigan | 9h-pyrimido [4,5-b]indoles as bet bromodomain inhibitors |
| GB201503720D0 (en) | 2015-03-05 | 2015-04-22 | Glaxosmithkline Ip No 2 Ltd | Chemical compound |
| GB201504689D0 (en) | 2015-03-19 | 2015-05-06 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| GB201504694D0 (en) | 2015-03-19 | 2015-05-06 | Glaxosmithkline Ip Dev Ltd | Covalent conjugates |
| TW201642860A (zh) * | 2015-04-22 | 2016-12-16 | 塞爾基因定量細胞研究公司 | 布羅莫結構域抑制劑 |
| US10702517B2 (en) | 2015-04-22 | 2020-07-07 | Celgene Quanticel Research, Inc. | Bromodomain inhibitor |
| WO2016196065A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Methods and compositions for assessing responsiveness of cancers to bet inhibitors |
| WO2016201370A1 (en) | 2015-06-12 | 2016-12-15 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| WO2016203335A1 (en) | 2015-06-18 | 2016-12-22 | Pfizer Inc. | Novel pyrido[2,3-b]pyrazinones as bet-family bromodomain inhibitors |
| MX2017016337A (es) | 2015-06-26 | 2018-11-22 | Tensha Therapeutics Inc | Tratamiento de carcinoma de linea media nut. |
| EP3334725B1 (en) | 2015-08-10 | 2025-04-23 | Dana-Farber Cancer Institute, Inc. | Bromodomain and extra terminal (bet) inhibitor and a protein phosphatase 2a (pp2a) activator for treating bet inhibitor resistant cancer |
| EA033679B1 (ru) | 2015-09-02 | 2019-11-15 | Glaxosmithkline Ip No 2 Ltd | Пиридинондикарбоксамиды для применения в качестве ингибиторов бромодомена |
| HK1256419A1 (zh) | 2015-09-11 | 2019-09-20 | 达纳-法伯癌症研究所股份有限公司 | 乙酰胺噻吩並三唑並二氮雜環庚三烯及其用途 |
| PE20181287A1 (es) | 2015-09-11 | 2018-08-07 | Dana Farber Cancer Inst Inc | Ciano tienotriazolpirazinas y usos de las mismas |
| JP6795588B2 (ja) | 2015-09-22 | 2020-12-02 | グラクソスミスクライン、インテレクチュアル、プロパティー、（ナンバー２）、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ （Ｎｏ．２） Ｌｉｍｉｔｅｄ | ブロモドメイン阻害薬としての使用のためのピリジノンジカルボキサミド |
| ES2831322T3 (es) | 2015-10-05 | 2021-06-08 | Glaxosmithkline Ip No 2 Ltd | Compuestos de 2-oxo-1,2-dihidropiridin-3,5-dicarboxamida como inhibidores de bromodominios |
| US20170121347A1 (en) | 2015-10-29 | 2017-05-04 | Incyte Corporation | Amorphous solid form of a bet protein inhibitor |
| SG10201913450PA (en) | 2015-11-25 | 2020-03-30 | Dana Farber Cancer Inst Inc | Bivalent bromodomain inhibitors and uses thereof |
| ES2882066T3 (es) | 2016-02-15 | 2021-12-01 | Univ Michigan Regents | 1,4-oxazepinas fusionadas y análogos relacionados como inhibidores de bromodominio BET |
| JP7001614B2 (ja) | 2016-04-06 | 2022-02-03 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | リガンド依存性の標的タンパク質分解のための単官能性中間体 |
| JP7037500B2 (ja) | 2016-04-06 | 2022-03-16 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Ｍｄｍ２タンパク質分解剤 |
| AU2017245641A1 (en) | 2016-04-07 | 2018-09-13 | Glaxosmithkline Intellectual Property (No.2) Limited | Pyridyl derivatives as bromodomain inhibitors |
| WO2017174620A1 (en) | 2016-04-07 | 2017-10-12 | Glaxosmithkline Intellectual Property (No.2) Limited | Benzo[b]furans as bromodomain inhibitors |
| AU2017250076B2 (en) | 2016-04-12 | 2021-07-22 | The Regents Of The University Of Michigan | Bet protein degraders |
| SG11201808003RA (en) | 2016-04-15 | 2018-10-30 | Abbvie Inc | Bromodomain inhibitors |
| WO2017205536A2 (en) * | 2016-05-24 | 2017-11-30 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| CN109153646B (zh) | 2016-05-24 | 2022-08-02 | 葛兰素史克知识产权第二有限公司 | 作为溴结构域抑制剂的吡啶二甲酰胺衍生物 |
| CR20190027A (es) | 2016-06-20 | 2019-05-16 | Incyte Corp | Formas sólidas cristalinas de un inhibidor de bet |
| GB201614939D0 (en) | 2016-09-02 | 2016-10-19 | Glaxosmithkline Ip Dev Ltd | Crystalline hydrate |
| GB201614934D0 (en) | 2016-09-02 | 2016-10-19 | Glaxosmithkline Intellectual Property (No 2) Ltd | Chemical compounds |
| GB201614940D0 (en) | 2016-09-02 | 2016-10-19 | Glaxosmithkline Intellectual Property (No 2) Ltd | Chemical compounds |
| AU2017326171B2 (en) | 2016-09-13 | 2021-12-09 | The Regents Of The University Of Michigan | Fused 1,4-oxazepines as BET protein degraders |
| JP7035027B2 (ja) | 2016-09-13 | 2022-03-14 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Ｂｅｔタンパク質分解物質としての縮合１，４－ジアゼピン |
| AU2017345468B2 (en) * | 2016-10-20 | 2022-06-02 | Celgene Quanticel Research, Inc. | Bromodomain inhibitor |
| WO2018111805A1 (en) * | 2016-12-13 | 2018-06-21 | St. Jude Children's Research Hospital | Tetrahydroquinoline-based bromodomain inhibitors |
| WO2018144789A1 (en) | 2017-02-03 | 2018-08-09 | The Regents Of The University Of Michigan | Fused 1,4-diazepines as bet bromodomain inhibitors |
| GB201703282D0 (en) | 2017-03-01 | 2017-04-12 | Glaxosmithkline Intellectual Property (No 2) Ltd | Compounds |
| GB201716374D0 (en) * | 2017-10-06 | 2017-11-22 | Glaxosmithkline Intellectual Property (No 2) Ltd | Compounds |
| JOP20190192A1 (ar) * | 2017-03-01 | 2019-08-08 | Glaxosmithkline Ip No 2 Ltd | مشتقات بيرازول بوصفها مثبطات برومودومين |
| US11267822B2 (en) | 2017-09-13 | 2022-03-08 | The Regents Of The University Of Michigan | BET bromodomain protein degraders with cleavable linkers |
| GB201716369D0 (en) | 2017-10-06 | 2017-11-22 | Glaxosmithkline Intellectual Property (No 2) Ltd | Compounds |
| GB201716392D0 (en) | 2017-10-06 | 2017-11-22 | Glaxosmithkline Intellectual Property (No 2) Ltd | Compounds |
| GB201814167D0 (en) | 2018-08-31 | 2018-10-17 | Glaxosmithkline Ip No 2 Ltd | Compounds |
| TWI882964B (zh) | 2018-09-13 | 2025-05-11 | 大陸商恒翼生物醫藥（上海）股份有限公司 | Bet 溴結構域(bromodomain)抑制劑之固體形式之製備方法 |
| TWI816880B (zh) * | 2018-09-13 | 2023-10-01 | 大陸商恒翼生物醫藥（上海）股份有限公司 | 治療前列腺癌之組合療法 |
| WO2021175432A1 (en) | 2020-03-04 | 2021-09-10 | Boehringer Ingelheim International Gmbh | Method for administration of an anti cancer agent |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| WO2023041744A1 (en) | 2021-09-17 | 2023-03-23 | Institut Curie | Bet inhibitors for treating pab1 deficient cancer |
| CA3255932A1 (en) | 2022-04-19 | 2023-10-26 | Nuevolution As | ACTIVE COMPOUNDS AGAINST BROMODOMAINS |
| WO2025049555A1 (en) | 2023-08-31 | 2025-03-06 | Oerth Bio Llc | Compositions and methods for targeted inhibition and degradation of proteins in an insect cell |
Family Cites Families (11)
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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 |
| US20050228016A1 (en) * | 2002-06-13 | 2005-10-13 | Enrique Michelotti | Tetrahydroquinolines for modulating the expression of exogenous genes via an ecdysone receptor complex |
| EP1435356A1 (en) * | 2003-01-06 | 2004-07-07 | Warner-Lambert Company LLC | Quinoline derivatives as CRTH2 antagonists |
| BRPI0416128B8 (pt) | 2003-11-03 | 2021-06-22 | Glaxo Group Ltd | dispositivo de dispensação de fluido |
| WO2006083692A2 (en) * | 2005-01-28 | 2006-08-10 | Mount Sinai Schoool Of Medicine | Methods of identifying modulators of bromodomains |
| 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 |
| US20100222347A1 (en) | 2007-09-27 | 2010-09-02 | Kowa Company, Ltd. | Prophylactic and/or therapeutic agent for anemia, comprising tetrahydroquinoline compound as active ingredient |
| KR101600634B1 (ko) | 2007-12-28 | 2016-03-07 | 미쓰비시 타나베 파마 코퍼레이션 | 항암제 |
| WO2010113498A1 (ja) | 2009-03-31 | 2010-10-07 | 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 |
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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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| EP2496558B1 (en) | 2016-03-30 |
| GB0919434D0 (en) | 2009-12-23 |
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| US8580957B2 (en) | 2013-11-12 |
| WO2011054848A1 (en) | 2011-05-12 |
| US20120208814A1 (en) | 2012-08-16 |
| EP2496558A1 (en) | 2012-09-12 |
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