RU2015148359A - Хиназолины и азахиназолины - двойные ингибиторы путей ras/raf/mek/erk и pi3k/akt/pten/mtor - Google Patents
Хиназолины и азахиназолины - двойные ингибиторы путей ras/raf/mek/erk и pi3k/akt/pten/mtor Download PDFInfo
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- RU2015148359A RU2015148359A RU2015148359A RU2015148359A RU2015148359A RU 2015148359 A RU2015148359 A RU 2015148359A RU 2015148359 A RU2015148359 A RU 2015148359A RU 2015148359 A RU2015148359 A RU 2015148359A RU 2015148359 A RU2015148359 A RU 2015148359A
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- Russia
- Prior art keywords
- sulfonamide
- fluorophenyl
- morpholinoquinazolin
- methoxy
- pyrimidin
- Prior art date
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- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 title claims 8
- 108091007960 PI3Ks Proteins 0.000 title claims 8
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 title claims 6
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 title claims 6
- 101150097381 Mtor gene Proteins 0.000 title 1
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 title 1
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- 150000003246 quinazolines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 33
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- 229910052736 halogen Inorganic materials 0.000 claims 9
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- HQOFCYFPTWLSNU-UHFFFAOYSA-N 1-[4-[6-[2-fluoro-3-(propylsulfonylamino)phenyl]-8-methoxy-4-morpholin-4-ylquinazolin-2-yl]phenyl]-3-methylurea Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C=CC(NC(=O)NC)=CC=2)=C1F HQOFCYFPTWLSNU-UHFFFAOYSA-N 0.000 claims 1
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- YQOPNAOQGQSUHF-UHFFFAOYSA-N 1-propan-2-ylpyrrolidine Chemical class CC(C)N1CCCC1 YQOPNAOQGQSUHF-UHFFFAOYSA-N 0.000 claims 1
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- HUIYTCHPWYKQRE-UHFFFAOYSA-N N-[3-[2-(2-aminopyrimidin-5-yl)-8-methyl-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound Cc1cc(cc2c(nc(nc12)-c1cnc(N)nc1)N1CCOCC1)-c1cccc(NS(=O)(=O)CCCF)c1F HUIYTCHPWYKQRE-UHFFFAOYSA-N 0.000 claims 1
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- LFAONIZWKJTNQP-HNNXBMFYSA-N N-[3-[2-(6-amino-4-fluoropyridin-3-yl)-4-[(3S)-3-methylmorpholin-4-yl]pyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C[C@H]1COCCN1c1nc(nc2ccc(nc12)-c1cccc(NS(=O)(=O)CCCF)c1F)-c1cnc(N)cc1F LFAONIZWKJTNQP-HNNXBMFYSA-N 0.000 claims 1
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- KWKYMTIODSCPKX-UHFFFAOYSA-N N-[3-[2-(6-aminopyridin-3-yl)-8-methyl-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound Cc1cc(cc2c(nc(nc12)-c1ccc(N)nc1)N1CCOCC1)-c1cccc(NS(=O)(=O)CCCF)c1F KWKYMTIODSCPKX-UHFFFAOYSA-N 0.000 claims 1
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- QQLNZBWHUXSJHO-UHFFFAOYSA-N n-[3-[2-(6-amino-5-methylpyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C=C(C)C(N)=NC=2)=C1F QQLNZBWHUXSJHO-UHFFFAOYSA-N 0.000 claims 1
- XZYPXLUJJDOHHD-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4,8-dimorpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(C=C(C=C2N3CCOCC3)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C2=N1 XZYPXLUJJDOHHD-UHFFFAOYSA-N 0.000 claims 1
- PGOQLDYCVFCOIQ-HXUWFJFHSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-[(3r)-3-methylmorpholin-4-yl]-8-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C[C@@H]1COCCN1C1=NC(C=2C=NC(N)=CC=2)=NC2=C(N3CCOCC3)C=C(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C=C12 PGOQLDYCVFCOIQ-HXUWFJFHSA-N 0.000 claims 1
- IEHHNERSWWKFMA-LJQANCHMSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-[(3r)-3-methylmorpholin-4-yl]-8-propan-2-yloxyquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC(C)C)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2[C@@H](COCC2)C)N=C1C1=CC=C(N)N=C1 IEHHNERSWWKFMA-LJQANCHMSA-N 0.000 claims 1
- IOPPHACWXKLSDE-MRXNPFEDSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-[(3r)-3-methylmorpholin-4-yl]pyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C[C@@H]1COCCN1C1=NC(C=2C=NC(N)=CC=2)=NC2=CC=C(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)N=C12 IOPPHACWXKLSDE-MRXNPFEDSA-N 0.000 claims 1
- JZBIKMAGUGEITA-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-yl-8-propan-2-yloxyquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC(C)C)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 JZBIKMAGUGEITA-UHFFFAOYSA-N 0.000 claims 1
- JULZXZPLIIQFRU-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-yl-8-pyrrolidin-1-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(C=C(C=C2N3CCCC3)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C2=N1 JULZXZPLIIQFRU-UHFFFAOYSA-N 0.000 claims 1
- ZAOUBHISQLGCCN-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(N=C(C=C2)C=3C(=C(NS(=O)(=O)C=4C(=CC=C(F)C=4)F)C=CC=3)F)C2=N1 ZAOUBHISQLGCCN-UHFFFAOYSA-N 0.000 claims 1
- YBYHVBPIMGMRRM-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(N=C(C=C2)C=3C(=C(NS(=O)(=O)C=4C(=CC=CC=4F)F)C=CC=3)F)C2=N1 YBYHVBPIMGMRRM-UHFFFAOYSA-N 0.000 claims 1
- GZXPIRAVIANAFR-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(N=C(C=C2)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C2=N1 GZXPIRAVIANAFR-UHFFFAOYSA-N 0.000 claims 1
- LKQRACJFAPDYAG-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2N=C3C(N4CCOCC4)=NC(=NC3=CC=2)C=2C=NC(N)=CC=2)=C1F LKQRACJFAPDYAG-UHFFFAOYSA-N 0.000 claims 1
- DWOHUURGSMGCTN-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(C=C(C=C2)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C2=N1 DWOHUURGSMGCTN-UHFFFAOYSA-N 0.000 claims 1
- UHBRXHHPAFDDNN-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-(2-hydroxyethoxy)-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OCCO)C=2)C=2C=NC(N)=CC=2)=C1F UHBRXHHPAFDDNN-UHFFFAOYSA-N 0.000 claims 1
- HORGZGMOHDXHCW-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-(2-methoxyethoxy)-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OCCOC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 HORGZGMOHDXHCW-UHFFFAOYSA-N 0.000 claims 1
- OFHLDVZCBNBQHY-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-(cyclopropylmethoxy)-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C1=NC(N)=CC=C1C1=NC(N2CCOCC2)=C(C=C(C=C2OCC3CC3)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C2=N1 OFHLDVZCBNBQHY-UHFFFAOYSA-N 0.000 claims 1
- SOALWTBJSNZFFE-HXUWFJFHSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-cyclopentyloxy-4-[(3r)-3-methylmorpholin-4-yl]quinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C[C@@H]1COCCN1C(C1=CC(=C2)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=NC(C=3C=NC(N)=CC=3)=NC1=C2OC1CCCC1 SOALWTBJSNZFFE-HXUWFJFHSA-N 0.000 claims 1
- SNPBKAXZGYXTBJ-SFHVURJKSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-ethoxy-4-[(3s)-3-methylmorpholin-4-yl]quinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OCC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2[C@H](COCC2)C)N=C1C1=CC=C(N)N=C1 SNPBKAXZGYXTBJ-SFHVURJKSA-N 0.000 claims 1
- HYAZGKVOQNPTBA-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-ethoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OCC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 HYAZGKVOQNPTBA-UHFFFAOYSA-N 0.000 claims 1
- UFYYJVISROPNGY-QGZVFWFLSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-[(3r)-3-methylmorpholin-4-yl]quinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2[C@@H](COCC2)C)N=C1C1=CC=C(N)N=C1 UFYYJVISROPNGY-QGZVFWFLSA-N 0.000 claims 1
- UFYYJVISROPNGY-KRWDZBQOSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-[(3s)-3-methylmorpholin-4-yl]quinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2[C@H](COCC2)C)N=C1C1=CC=C(N)N=C1 UFYYJVISROPNGY-KRWDZBQOSA-N 0.000 claims 1
- LGRAJMABIRPGLF-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2,4-difluorophenyl]-2,5-difluorobenzenesulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)C=4C(=CC=C(F)C=4)F)C=CC=3F)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 LGRAJMABIRPGLF-UHFFFAOYSA-N 0.000 claims 1
- CEPAMBLVDZAOSB-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2,4-difluorophenyl]-2,6-difluorobenzenesulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)C=4C(=CC=CC=4F)F)C=CC=3F)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 CEPAMBLVDZAOSB-UHFFFAOYSA-N 0.000 claims 1
- CRJSYOVFXUPDHL-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2,4-difluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3F)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 CRJSYOVFXUPDHL-UHFFFAOYSA-N 0.000 claims 1
- KYHPQTWHJQMQGQ-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2,4-difluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C=NC(N)=CC=2)=C1F KYHPQTWHJQMQGQ-UHFFFAOYSA-N 0.000 claims 1
- YFNDQLJYZBTTJM-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)C=4C(=CC=C(F)C=4)F)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 YFNDQLJYZBTTJM-UHFFFAOYSA-N 0.000 claims 1
- IEDUKQBJHRARBP-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-2-fluorobenzenesulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)C=4C(=CC=CC=4)F)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 IEDUKQBJHRARBP-UHFFFAOYSA-N 0.000 claims 1
- HELYTTFCDKGKRA-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3,3,3-trifluoropropane-1-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)CCC(F)(F)F)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 HELYTTFCDKGKRA-UHFFFAOYSA-N 0.000 claims 1
- HXHFPQBIAHMONW-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 HXHFPQBIAHMONW-UHFFFAOYSA-N 0.000 claims 1
- XKCMCAARLGTTHK-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C=NC(N)=CC=2)=C1F XKCMCAARLGTTHK-UHFFFAOYSA-N 0.000 claims 1
- FXYHCEPZBOEABL-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-2-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)C(C)C)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 FXYHCEPZBOEABL-UHFFFAOYSA-N 0.000 claims 1
- WRPOFWXOHPGVMB-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]thiophene-2-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)C=4SC=CC=4)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 WRPOFWXOHPGVMB-UHFFFAOYSA-N 0.000 claims 1
- XZIQCBUDUDNDEV-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-4-chloro-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=C(Cl)C(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C=NC(N)=CC=2)=C1F XZIQCBUDUDNDEV-UHFFFAOYSA-N 0.000 claims 1
- GBZBHGCSKIUCSA-UHFFFAOYSA-N n-[3-[2-(6-aminopyridin-3-yl)-8-methyl-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(C)C=2)C=2C=NC(N)=CC=2)=C1F GBZBHGCSKIUCSA-UHFFFAOYSA-N 0.000 claims 1
- QAPKBGXCXBKSAH-UHFFFAOYSA-N n-[3-[2-[2-amino-4-(trifluoromethyl)pyrimidin-5-yl]-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound FC(F)(F)C1=NC(N)=NC=C1C1=NC(N2CCOCC2)=C(N=C(C=C2)C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)C2=N1 QAPKBGXCXBKSAH-UHFFFAOYSA-N 0.000 claims 1
- VGSGDGSPVDLAGZ-UHFFFAOYSA-N n-[3-[2-[6-(2-aminoethylamino)pyridin-3-yl]-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C=NC(NCCN)=CC=2)=C1F VGSGDGSPVDLAGZ-UHFFFAOYSA-N 0.000 claims 1
- SAWOLQUFBIQXMM-OAHLLOKOSA-N n-[3-[2-[6-amino-4-(trifluoromethyl)pyridin-3-yl]-4-[(3r)-3-methylmorpholin-4-yl]pyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C[C@@H]1COCCN1C1=NC(C=2C(=CC(N)=NC=2)C(F)(F)F)=NC2=CC=C(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)N=C12 SAWOLQUFBIQXMM-OAHLLOKOSA-N 0.000 claims 1
- SAWOLQUFBIQXMM-HNNXBMFYSA-N n-[3-[2-[6-amino-4-(trifluoromethyl)pyridin-3-yl]-4-[(3s)-3-methylmorpholin-4-yl]pyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound C[C@H]1COCCN1C1=NC(C=2C(=CC(N)=NC=2)C(F)(F)F)=NC2=CC=C(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)N=C12 SAWOLQUFBIQXMM-HNNXBMFYSA-N 0.000 claims 1
- OJSLRDMDAJNKNY-UHFFFAOYSA-N n-[3-[2-[6-amino-4-(trifluoromethyl)pyridin-3-yl]-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=NC(N2CCOCC2)=C(N=C(C=C2)C=3C(=C(NS(=O)(=O)C=4C(=CC=C(F)C=4)F)C=CC=3)F)C2=N1 OJSLRDMDAJNKNY-UHFFFAOYSA-N 0.000 claims 1
- KFIUUZXVKZLMHO-UHFFFAOYSA-N n-[3-[2-[6-amino-4-(trifluoromethyl)pyridin-3-yl]-4-morpholin-4-ylpyrido[3,2-d]pyrimidin-6-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=NC(N2CCOCC2)=C(N=C(C=C2)C=3C(=C(NS(=O)(=O)C=4C(=CC=CC=4F)F)C=CC=3)F)C2=N1 KFIUUZXVKZLMHO-UHFFFAOYSA-N 0.000 claims 1
- JFLNSIYWLXFIHE-UHFFFAOYSA-N n-[3-[2-[6-amino-4-(trifluoromethyl)pyridin-3-yl]-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CN=C(N)C=C1C(F)(F)F JFLNSIYWLXFIHE-UHFFFAOYSA-N 0.000 claims 1
- NCULONDURABZAN-UHFFFAOYSA-N n-[3-[2-[6-amino-4-(trifluoromethyl)pyridin-3-yl]-8-methoxy-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C=C3C(N4CCOCC4)=NC(=NC3=C(OC)C=2)C=2C(=CC(N)=NC=2)C(F)(F)F)=C1F NCULONDURABZAN-UHFFFAOYSA-N 0.000 claims 1
- JMSLSWNGLUWSGI-UHFFFAOYSA-N n-[3-[8-(2-aminoethoxy)-2-(6-aminopyridin-3-yl)-4-morpholin-4-ylquinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C2C(OCCN)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C(N2CCOCC2)N=C1C1=CC=C(N)N=C1 JMSLSWNGLUWSGI-UHFFFAOYSA-N 0.000 claims 1
- RRCKEUACSSHIDV-LJQANCHMSA-N n-[3-[8-ethoxy-4-[(3r)-3-methylmorpholin-4-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yl)quinazolin-6-yl]-2-fluorophenyl]-3-fluoropropane-1-sulfonamide Chemical compound N1=C(C=2C=C3C=CNC3=NC=2)N=C2C(OCC)=CC(C=3C(=C(NS(=O)(=O)CCCF)C=CC=3)F)=CC2=C1N1CCOC[C@H]1C RRCKEUACSSHIDV-LJQANCHMSA-N 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 150000003222 pyridines Chemical class 0.000 claims 1
- 150000003230 pyrimidines Chemical class 0.000 claims 1
- 150000003233 pyrroles Chemical class 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- 229930192474 thiophene Natural products 0.000 claims 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-O triethanolammonium Chemical compound OCC[NH+](CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-O 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 claims 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims 1
- DRDCQJADRSJFFD-UHFFFAOYSA-N tris-hydroxymethyl-methyl-ammonium Chemical compound OC[N+](C)(CO)CO DRDCQJADRSJFFD-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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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
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57496—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving intracellular compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| US201361811408P | 2013-04-12 | 2013-04-12 | |
| US61/811,408 | 2013-04-12 | ||
| PCT/US2014/033727 WO2014169167A1 (en) | 2013-04-12 | 2014-04-11 | Quinazolines and azaquinazolines as dual inhibitors of ras/raf/mek/erk and pi3k/akt/pten/mtor pathways |
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| RU2015148359A true RU2015148359A (ru) | 2017-05-15 |
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| US10221191B2 (en) | 2015-12-22 | 2019-03-05 | SHY Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| EP4086250B1 (en) * | 2016-07-06 | 2024-12-11 | The Regents Of The University Of Michigan | Multifunctional inhibitors of mek/pi3k and mtor/mek/pi3k biological pathways and therapeutic methods using the same |
| EP3560921B1 (en) * | 2016-12-26 | 2024-08-14 | Institute Of Materia Medica, Chinese Academy Of Medical Sciences | Quinazoline compound, preparation method, application as pi3k inhibitor for the treatment of cancer, and pharmaceutical compostion thereof |
| CN108239074B (zh) * | 2016-12-26 | 2021-07-06 | 中国医学科学院药物研究所 | 喹唑啉类化合物及其制备方法、用途和药物组合物 |
| CN108239076B (zh) * | 2016-12-26 | 2021-07-06 | 中国医学科学院药物研究所 | 喹唑啉类化合物及其制备方法、用途和药物组合物 |
| CN108239075B (zh) * | 2016-12-26 | 2021-07-02 | 中国医学科学院药物研究所 | 喹唑啉类化合物及其制备方法、用途和药物组合物 |
| WO2018212774A1 (en) * | 2017-05-17 | 2018-11-22 | Vanderbilt University | Quinazoline compounds as modulators of ras signaling |
| SG11201911929XA (en) | 2017-06-21 | 2020-01-30 | SHY Therapeutics LLC | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| WO2019014668A1 (en) * | 2017-07-14 | 2019-01-17 | Asana Biosciences, Llc | FORMULATIONS, METHODS, KIT AND DOSAGE FORMS FOR ENHANCED STABILITY OF ACTIVE PHARMACEUTICAL INGREDIENT |
| CN108623582A (zh) * | 2017-10-10 | 2018-10-09 | 河南省锐达医药科技有限公司 | 一类新型含取代基吡啶并嘧啶化合物的制备方法 |
| WO2020132071A1 (en) | 2018-12-19 | 2020-06-25 | Shy Therapeutics. Llc | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and f1brotic disease |
| CN111499634B (zh) * | 2019-01-31 | 2023-05-12 | 贝达药业股份有限公司 | 一种喹唑啉化合物及其在医药上的应用 |
| CN112341434B (zh) * | 2019-08-08 | 2021-11-26 | 恩瑞生物医药科技（上海）有限公司 | PI3K/mTOR蛋白降解靶向嵌合体类化合物及其制备方法和医药用途 |
| BR112022008061A2 (pt) | 2019-11-01 | 2022-07-12 | Fmc Corp | Processo eficaz para síntese de 2-amino-5-cloro-n,3-dimetilbenzamida |
| CA3159561A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| IL301298A (en) | 2020-09-15 | 2023-05-01 | Revolution Medicines Inc | Indole derivatives as RAS inhibitors in cancer therapy |
| JP2023549540A (ja) * | 2020-11-18 | 2023-11-27 | デシフェラ・ファーマシューティカルズ，エルエルシー | Ｇｃｎ２およびｐｅｒｋキナーゼ阻害剤およびその使用方法 |
| WO2022235870A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
| CN113416181B (zh) * | 2021-08-02 | 2022-05-03 | 四川大学 | 喹唑啉类衍生物及其用途 |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| WO2023131122A1 (zh) * | 2022-01-04 | 2023-07-13 | 劲方医药科技(上海)有限公司 | 稠环取代的六元杂环化合物及其制法和用途 |
| CN115894211A (zh) * | 2022-11-10 | 2023-04-04 | 山东龙立恒医药有限公司 | 一种3-羟基-4-甲基苯甲酸的制备方法 |
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| GB0428475D0 (en) | 2004-12-30 | 2005-02-02 | 4 Aza Bioscience Nv | Pyrido(3,2-D)pyrimidine derivatives and pharmaceutical compositions useful as medicines for the treatment of autoimmune disorders |
| GB0503506D0 (en) | 2005-02-21 | 2005-03-30 | 4 Aza Bioscience Nv | Substituted pyrido(2,3-d) pyrimidine derivatives and pharmaceutical compositions useful as medicines for the treatment of autoimmune disorders |
| KR101402474B1 (ko) | 2006-04-26 | 2014-06-19 | 제넨테크, 인크. | 포스포이노시티드 3-키나제 억제제 화합물 및 이를 포함하는 약학적 조성물 |
| UY31137A1 (es) * | 2007-06-14 | 2009-01-05 | Smithkline Beecham Corp | Derivados de quinazolina como inhibidores de la pi3 quinasa |
| EP2217590A4 (en) * | 2007-09-17 | 2011-12-14 | Glaxosmithkline Llc | Pyridopyrimidine derivatives as PI3-kinase inhibitors |
| CA2716826C (en) * | 2008-02-25 | 2017-05-09 | Prometheus Laboratories Inc. | Drug selection for breast cancer therapy using antibody-based arrays |
| WO2010037765A2 (en) * | 2008-10-03 | 2010-04-08 | Merck Serono S.A. | 4-morpholino-pyrido[3,2-d]pyrimidines |
| US9181238B2 (en) * | 2010-02-05 | 2015-11-10 | Novartis Ag | N-(pyridin-2-yl)sulfonamides and compositions thereof as protein kinase inhibitors |
| MX2012009059A (es) | 2010-02-22 | 2012-09-07 | Hoffmann La Roche | Compuestos inhibidores de fosfoinositida 3-cinasa delta (pi3k) pirido [3,2-d]pirimidina y metodos de uso. |
| WO2012118492A1 (en) * | 2011-03-01 | 2012-09-07 | Array Biopharma Inc. | Heterocyclic sulfonamides as raf inhibitors |
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| JP6496301B2 (ja) | 2019-04-03 |
| EP2984088B1 (en) | 2019-03-20 |
| AU2014250836C1 (en) | 2019-01-17 |
| IL262314A (en) | 2018-11-29 |
| BR112015025901A8 (pt) | 2020-01-14 |
| CA2909310A1 (en) | 2014-10-16 |
| US20210113578A1 (en) | 2021-04-22 |
| CN105283454A (zh) | 2016-01-27 |
| US20170027953A1 (en) | 2017-02-02 |
| BR112015025901A2 (pt) | 2017-07-25 |
| AU2014250836B2 (en) | 2018-07-12 |
| ZA201507750B (en) | 2017-08-30 |
| WO2014169167A1 (en) | 2014-10-16 |
| US10912779B2 (en) | 2021-02-09 |
| EP2984088A1 (en) | 2016-02-17 |
| AU2014250836A1 (en) | 2015-11-26 |
| US20170290838A1 (en) | 2017-10-12 |
| MX2015014387A (es) | 2017-04-10 |
| US20160068496A1 (en) | 2016-03-10 |
| KR20150143672A (ko) | 2015-12-23 |
| US9757382B2 (en) | 2017-09-12 |
| IL242020B (en) | 2019-08-29 |
| CN105283454B (zh) | 2019-10-29 |
| US9499495B2 (en) | 2016-11-22 |
| HK1215810A1 (en) | 2016-09-15 |
| US20190151327A1 (en) | 2019-05-23 |
| JP2016519685A (ja) | 2016-07-07 |
| US10226468B2 (en) | 2019-03-12 |
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