AU2008269577B2 - Fused thiazole derivatives as kinase inhibitors - Google Patents
Fused thiazole derivatives as kinase inhibitors Download PDFInfo
- Publication number
- AU2008269577B2 AU2008269577B2 AU2008269577A AU2008269577A AU2008269577B2 AU 2008269577 B2 AU2008269577 B2 AU 2008269577B2 AU 2008269577 A AU2008269577 A AU 2008269577A AU 2008269577 A AU2008269577 A AU 2008269577A AU 2008269577 B2 AU2008269577 B2 AU 2008269577B2
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- alkyl
- dimethyl
- morpholin
- thiazolo
- 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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- 150000007979 thiazole derivatives Chemical class 0.000 title description 4
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 230000001363 autoimmune Effects 0.000 claims abstract description 7
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 7
- 230000002503 metabolic effect Effects 0.000 claims abstract description 7
- 230000003040 nociceptive effect Effects 0.000 claims abstract description 7
- 230000000771 oncological effect Effects 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 6
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 6
- -1 arylsulphinyl Chemical group 0.000 claims description 183
- 150000001875 compounds Chemical class 0.000 claims description 150
- 238000000034 method Methods 0.000 claims description 133
- 125000000217 alkyl group Chemical group 0.000 claims description 100
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 239000003112 inhibitor Substances 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 7
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 150000002923 oximes Chemical class 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000005968 oxazolinyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 6
- JVSGBNZVDWHFDO-KRWDZBQOSA-N 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-n,n,1-trimethylindole-5-carboxamide Chemical compound C1C(C)(C)NC(=O)C(S2)=C1N=C2N1CCOC[C@@H]1CC1=CN(C)C2=CC=C(C(=O)N(C)C)C=C21 JVSGBNZVDWHFDO-KRWDZBQOSA-N 0.000 claims 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- BTSXTRLPRJVJSW-UHFFFAOYSA-N 1,2,3-trimethylindole-5-carboxamide Chemical compound NC(=O)C1=CC=C2N(C)C(C)=C(C)C2=C1 BTSXTRLPRJVJSW-UHFFFAOYSA-N 0.000 claims 1
- JUXXWKDPXCWDEA-AWEZNQCLSA-N 2-[(3s)-3-(1-benzofuran-3-ylmethyl)morpholin-4-yl]-6,6-dimethyl-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4-one Chemical compound C1=CC=C2C(C[C@H]3COCCN3C3=NC=4CC(NC(=O)C=4S3)(C)C)=COC2=C1 JUXXWKDPXCWDEA-AWEZNQCLSA-N 0.000 claims 1
- UHLCUNGGYHSGQK-KRWDZBQOSA-N 2-[(3s)-3-[[5-(azetidine-1-carbonyl)-1-benzofuran-3-yl]methyl]morpholin-4-yl]-6,6-dimethyl-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4-one Chemical compound C([C@H]1COCCN1C1=NC=2CC(NC(=O)C=2S1)(C)C)C(C1=C2)=COC1=CC=C2C(=O)N1CCC1 UHLCUNGGYHSGQK-KRWDZBQOSA-N 0.000 claims 1
- ZFCOZWRXIYETAF-SFHVURJKSA-N 2-[(3s)-3-[[5-(azetidine-1-carbonyl)-1-methylindol-3-yl]methyl]morpholin-4-yl]-6,6-dimethyl-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4-one Chemical compound C=1C=C2N(C)C=C(C[C@@H]3N(CCOC3)C=3SC=4C(=O)NC(C)(C)CC=4N=3)C2=CC=1C(=O)N1CCC1 ZFCOZWRXIYETAF-SFHVURJKSA-N 0.000 claims 1
- KOGQXIYBCBOANV-HNNXBMFYSA-N 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-1-benzofuran-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(C[C@H]3COCCN3C3=NC=4CC(NC(=O)C=4S3)(C)C)=COC2=C1 KOGQXIYBCBOANV-HNNXBMFYSA-N 0.000 claims 1
- UBZDDEORUSXHDB-INIZCTEOSA-N 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-1-methylindole-5-carbonitrile Chemical compound C12=CC(C#N)=CC=C2N(C)C=C1C[C@@H]1N(C=2SC=3C(=O)NC(C)(C)CC=3N=2)CCOC1 UBZDDEORUSXHDB-INIZCTEOSA-N 0.000 claims 1
- VMBRTLHHKDIASO-HNNXBMFYSA-N 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-1-methylindole-5-carboxylic acid Chemical compound C12=CC(C(O)=O)=CC=C2N(C)C=C1C[C@@H]1N(C=2SC=3C(=O)NC(C)(C)CC=3N=2)CCOC1 VMBRTLHHKDIASO-HNNXBMFYSA-N 0.000 claims 1
- BROYDOKGPFHXGG-INIZCTEOSA-N 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-n,n-dimethyl-1-benzofuran-5-carboxamide Chemical compound C1C(C)(C)NC(=O)C(S2)=C1N=C2N1CCOC[C@@H]1CC1=COC2=CC=C(C(=O)N(C)C)C=C21 BROYDOKGPFHXGG-INIZCTEOSA-N 0.000 claims 1
- IFSNARYYAQCALM-IBGZPJMESA-N 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-n-(2-methoxyethyl)-n,1-dimethylindole-5-carboxamide Chemical compound C1C(C)(C)NC(=O)C(S2)=C1N=C2N1CCOC[C@@H]1CC1=CN(C)C2=CC=C(C(=O)N(C)CCOC)C=C21 IFSNARYYAQCALM-IBGZPJMESA-N 0.000 claims 1
- KZHJXPFTTKZVJU-HNNXBMFYSA-N 6,6-dimethyl-2-[(3s)-3-[(1-methylindol-3-yl)methyl]morpholin-4-yl]-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4-one Chemical compound C12=CC=CC=C2N(C)C=C1C[C@@H]1N(C=2SC=3C(=O)NC(C)(C)CC=3N=2)CCOC1 KZHJXPFTTKZVJU-HNNXBMFYSA-N 0.000 claims 1
- XEYXAAAKLHDYBZ-HNNXBMFYSA-N methyl 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-1-benzofuran-5-carboxylate Chemical compound C1C(C)(C)NC(=O)C(S2)=C1N=C2N1CCOC[C@@H]1CC1=COC2=CC=C(C(=O)OC)C=C21 XEYXAAAKLHDYBZ-HNNXBMFYSA-N 0.000 claims 1
- VQYMPSODBDRLMV-INIZCTEOSA-N methyl 3-[[(3s)-4-(6,6-dimethyl-4-oxo-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)morpholin-3-yl]methyl]-1-methylindole-5-carboxylate Chemical compound C1C(C)(C)NC(=O)C(S2)=C1N=C2N1CCOC[C@@H]1CC1=CN(C)C2=CC=C(C(=O)OC)C=C21 VQYMPSODBDRLMV-INIZCTEOSA-N 0.000 claims 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 abstract description 8
- 230000008901 benefit Effects 0.000 abstract description 4
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract description 2
- QGUSXKFSPVAZOB-UHFFFAOYSA-N 6,7-dihydro-5h-[1,3]thiazolo[5,4-c]pyridin-4-one Chemical class O=C1NCCC2=C1SC=N2 QGUSXKFSPVAZOB-UHFFFAOYSA-N 0.000 abstract 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 117
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
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- 239000000243 solution Substances 0.000 description 48
- 239000007787 solid Substances 0.000 description 46
- 229910004298 SiO 2 Inorganic materials 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
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- 238000006243 chemical reaction Methods 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 14
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
- 235000019253 formic acid Nutrition 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
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- 238000003756 stirring Methods 0.000 description 10
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 9
- 239000012223 aqueous fraction Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
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- 239000002253 acid Substances 0.000 description 7
- 125000004414 alkyl thio group Chemical group 0.000 description 7
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- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 7
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- 125000001424 substituent group Chemical group 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
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- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 6
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- 238000002953 preparative HPLC Methods 0.000 description 6
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
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- 239000007788 liquid Substances 0.000 description 5
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 5
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- 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 description 4
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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| GB0620062A GB0620062D0 (en) | 2006-10-10 | 2006-10-10 | Therapeutic agents |
| PCT/GB2007/002390 WO2008001076A1 (en) | 2006-06-26 | 2007-06-26 | Fused thiazole derivatives as kinase inhibitors |
| AUPCT/GB2007/002390 | 2007-06-26 | ||
| PCT/GB2008/002194 WO2009001089A1 (en) | 2007-06-26 | 2008-06-24 | Fused thiazole derivatives as kinase inhibitors |
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| WO2009071895A1 (en) * | 2007-12-04 | 2009-06-11 | Ucb Pharma S.A. | Fused thiazole and thiophene derivatives as kinase inhibitors |
| WO2009071890A1 (en) * | 2007-12-04 | 2009-06-11 | Ucb Pharma S.A. | Tricyclic kinase inhibitors |
| EP2231656A1 (en) | 2007-12-19 | 2010-09-29 | Amgen Inc. | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
| EP2278973B1 (en) | 2008-04-07 | 2011-11-02 | Amgen Inc. | Gem-disubstituted and spirocyclic amino pyridines/pyrimidines as cell cycle inhibitors |
| WO2009130900A1 (ja) * | 2008-04-24 | 2009-10-29 | 日本曹達株式会社 | オキシム誘導体、中間体化合物および植物病害防除剤 |
| US8603945B2 (en) * | 2008-07-23 | 2013-12-10 | The Regents Of The University Of California | Methods and compositions for providing salicyclic acid-independent pathogen resistance in plants |
| WO2010027002A1 (ja) * | 2008-09-05 | 2010-03-11 | 塩野義製薬株式会社 | Ｐｉ３ｋ阻害活性を有する縮環モルホリン誘導体 |
| CA2752596A1 (en) | 2009-02-17 | 2010-08-26 | Vertex Pharmaceuticals Incorporated | Tetrahydrothiazolopyridine inhibitors of phosphatidylinositol 3-kinase |
| CA2755253A1 (en) * | 2009-03-18 | 2010-09-23 | Schering Corporation | Bicyclic compounds as inhibitors of diacylglycerol acyltransferase |
| UY32582A (es) * | 2009-04-28 | 2010-11-30 | Amgen Inc | Inhibidores de fosfoinositida 3 cinasa y/u objetivo mamífero |
| WO2010135504A1 (en) | 2009-05-20 | 2010-11-25 | Glaxosmithkline Llc | Thiazolopyrimidinone derivatives as pi3 kinase inhibitors |
| GB0912946D0 (en) | 2009-07-24 | 2009-09-02 | Addex Pharmaceuticals Sa | New compounds 5 |
| IN2012DN01325A (enExample) | 2009-08-20 | 2015-06-05 | Karus Therapeutics Ltd | |
| KR20120101551A (ko) * | 2009-12-18 | 2012-09-13 | 얀센 파마슈티카 엔.브이. | Ｍｇｌｕｒ５ 수용체의 알로스테릭 조절자로서 바이사이클릭 티아졸 |
| US9040707B2 (en) | 2009-12-18 | 2015-05-26 | Janssen Pharmaceutica Nv | Bicyclic thiazoles as allosteric modulators of mGluR5 receptors |
| MX2012014575A (es) | 2010-06-15 | 2013-02-07 | Bayer Ip Gmbh | Nuevos derivados de arilamida orto-sustituidos. |
| AR084486A1 (es) | 2010-10-01 | 2013-05-22 | Basf Se | Compuestos de imina |
| EP2627181A4 (en) * | 2010-10-13 | 2014-03-19 | Millennium Pharm Inc | HETEROARYLE AND USES THEREOF |
| EA201390759A1 (ru) * | 2010-11-24 | 2014-03-31 | Экселиксис, Инк. | БЕНЗОКСАЗЕПИНЫ КАК ИНГИБИТОРЫ mTOR И СПОСОБЫ ИХ ИСПОЛЬЗОВАНИЯ И ПРОИЗВОДСТВА |
| CN102649777B (zh) * | 2011-02-25 | 2014-03-12 | 中国中化股份有限公司 | 一种制备1-芳基-3-羧基-5-吡唑啉酮类化合物的方法 |
| ES2543569T3 (es) | 2011-03-23 | 2015-08-20 | Amgen Inc. | Inhibidores duales tricíclicos condensados de CDK 4/6 y FLT3 |
| HUE036953T2 (hu) | 2011-12-22 | 2018-08-28 | Novartis Ag | 2,3-dihidro-benzo[1,4]oxazin-származékok és rokon vegyületek, mint foszfoinozitid-3-kináz (PI3K) inhibitorok például reumatoid arthritis kezelésére |
| US20160039767A1 (en) | 2013-03-14 | 2016-02-11 | Epizyme, Inc. | Pyrazole derivatives as prmt1 inhibitors and uses thereof |
| WO2014153208A1 (en) | 2013-03-14 | 2014-09-25 | Epizyme, Inc. | Arginine methyltransferase inhibitors and uses thereof |
| EP2970135B1 (en) | 2013-03-14 | 2018-07-18 | Epizyme, Inc. | Pyrazole derivatives as prmt1 inhibitors and uses thereof |
| US9447079B2 (en) | 2013-03-14 | 2016-09-20 | Epizyme, Inc. | PRMT1 inhibitors and uses thereof |
| EP2970137A1 (en) | 2013-03-14 | 2016-01-20 | Epizyme, Inc. | Pyrazole derivatives as arginine methyltransferase inhibitors and uses thereof |
| US9120757B2 (en) | 2013-03-14 | 2015-09-01 | Epizyme, Inc. | Arginine methyltransferase inhibitors and uses thereof |
| LT2970132T (lt) | 2013-03-14 | 2021-01-11 | Epizyme, Inc. | Argininmetiltransferazės inhibitoriai ir jų panaudojimas |
| EP2970136A1 (en) | 2013-03-14 | 2016-01-20 | Epizyme, Inc. | Arginine methyl transferase inhibtors and uses thereof |
| WO2014153235A2 (en) | 2013-03-14 | 2014-09-25 | Epizyme, Inc. | Arginine methyltransferase inhibitors and uses thereof |
| EP3363434A1 (en) | 2013-03-14 | 2018-08-22 | Epizyme Inc | Arginine methyltransferase inhibitors and uses thereof |
| US20160257650A1 (en) * | 2013-10-21 | 2016-09-08 | Umicore Ag & Co. Kg | Monoarylation of aromatic amines |
| GB201402431D0 (en) | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| GB201514760D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| GB201514754D0 (en) * | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| WO2017156350A1 (en) | 2016-03-09 | 2017-09-14 | K-Gen, Inc. | Methods of cancer treatment |
| CN108570043A (zh) * | 2018-06-20 | 2018-09-25 | 王延娇 | 一种化合物及其作为选择性pi3k抑制剂在治疗肿瘤中的应用 |
| EP3849548A1 (en) | 2018-09-13 | 2021-07-21 | Stemline Therapeutics Inc. | Methods for treating centronuclear myopathy |
| MX2021006421A (es) | 2018-12-19 | 2021-08-16 | Leo Pharma As | Anilidas de aminoácidos como moduladores de moléculas pequeñas de interleucinas-17 (il-17). |
| IL283608B2 (en) * | 2019-01-08 | 2025-06-01 | Kyorin Pharmaceutical Co Ltd Co Number 0100 01 01479 | 15-PGDH inhibitor |
| JP7532385B2 (ja) | 2019-01-31 | 2024-08-13 | 杏林製薬株式会社 | １５－ｐｇｄｈ阻害薬 |
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| WO2006114606A1 (en) * | 2005-04-26 | 2006-11-02 | Ucb Pharma S.A. | Fused thiazole derivatives as kinase inhibitors |
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| WO2006114606A1 (en) * | 2005-04-26 | 2006-11-02 | Ucb Pharma S.A. | Fused thiazole derivatives as kinase inhibitors |
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| US20130079330A1 (en) | 2013-03-28 |
| EP2170906A1 (en) | 2010-04-07 |
| US8710054B2 (en) | 2014-04-29 |
| DK2170906T3 (da) | 2013-06-24 |
| CO6270229A2 (es) | 2011-04-20 |
| EA201000038A1 (ru) | 2010-06-30 |
| ES2365258T3 (es) | 2011-09-27 |
| EP2170906B1 (en) | 2013-04-03 |
| ES2416364T3 (es) | 2013-07-31 |
| ATE510840T1 (de) | 2011-06-15 |
| PT2170906E (pt) | 2013-06-25 |
| EA017187B1 (ru) | 2012-10-30 |
| MY148852A (en) | 2013-06-14 |
| IL202659A0 (en) | 2010-06-30 |
| CN101687885B (zh) | 2012-08-22 |
| RS52824B (enExample) | 2013-10-31 |
| CY1114419T1 (el) | 2016-08-31 |
| MX2009013740A (es) | 2010-02-01 |
| ME01592B (me) | 2014-09-20 |
| CA2692085A1 (en) | 2008-12-31 |
| WO2008001076A1 (en) | 2008-01-03 |
| CA2692085C (en) | 2015-10-13 |
| CN101687885A (zh) | 2010-03-31 |
| EP2035436B1 (en) | 2011-05-25 |
| PL2170906T3 (pl) | 2013-08-30 |
| US20110003785A1 (en) | 2011-01-06 |
| AU2008269577A1 (en) | 2008-12-31 |
| US8338592B2 (en) | 2012-12-25 |
| HRP20130523T1 (en) | 2013-07-31 |
| US20100137302A1 (en) | 2010-06-03 |
| US8242116B2 (en) | 2012-08-14 |
| EP2035436A1 (en) | 2009-03-18 |
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