JP2013523891A5 - - Google Patents
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- Publication number
- JP2013523891A5 JP2013523891A5 JP2013505087A JP2013505087A JP2013523891A5 JP 2013523891 A5 JP2013523891 A5 JP 2013523891A5 JP 2013505087 A JP2013505087 A JP 2013505087A JP 2013505087 A JP2013505087 A JP 2013505087A JP 2013523891 A5 JP2013523891 A5 JP 2013523891A5
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- oxo
- pyrimidinediamine
- pyrido
- oxazin
- 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.)
- Granted
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- 125000000217 alkyl group Chemical group 0.000 claims description 121
- -1 2-oxa-5-azabicyclo [2.2.1] heptanyl Chemical group 0.000 claims description 108
- 125000003118 aryl group Chemical group 0.000 claims description 89
- 150000001875 compounds Chemical class 0.000 claims description 80
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 68
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 55
- 150000002431 hydrogen Chemical class 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 40
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 25
- 125000004104 aryloxy group Chemical group 0.000 claims description 24
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- CJUIETFEBPSWEU-CYBMUJFWSA-N 6-[[5-fluoro-2-[[6-[(3r)-3-hydroxypyrrolidin-1-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CC[C@@H](O)C1 CJUIETFEBPSWEU-CYBMUJFWSA-N 0.000 claims description 6
- VIBOBCDICAAZKZ-ZDUSSCGKSA-N 6-[[5-fluoro-2-[[6-[(3s)-3-methylmorpholin-4-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C[C@H]1COCCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 VIBOBCDICAAZKZ-ZDUSSCGKSA-N 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- MMQMXAFTMMKGRN-ZDUSSCGKSA-N 6-[[5-fluoro-2-[[6-[(2s)-2-methylmorpholin-4-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1CO[C@@H](C)CN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 MMQMXAFTMMKGRN-ZDUSSCGKSA-N 0.000 claims description 5
- RYMXNBYSVABIPZ-CQSZACIVSA-N 6-[[5-fluoro-2-[[6-[(3r)-3-methoxypyrrolidin-1-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1[C@H](OC)CCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 RYMXNBYSVABIPZ-CQSZACIVSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 229910052717 sulfur Chemical group 0.000 claims description 5
- 239000011593 sulfur Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000005961 oxazepanyl group Chemical group 0.000 claims description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 231100000241 scar Toxicity 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- UNVFYFLPCKFDCE-UHFFFAOYSA-N 1-[5-[[4-[(2,2-dimethyl-3-oxo-4h-pyrido[3,2-b][1,4]oxazin-6-yl)amino]-5-fluoropyrimidin-2-yl]amino]pyridin-2-yl]pyrrolidine-3-carboxamide Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCC(C(N)=O)C1 UNVFYFLPCKFDCE-UHFFFAOYSA-N 0.000 claims description 3
- WPLSNJRTQSTZGY-UHFFFAOYSA-N 6-[[2-[[6-(2,2-dimethylmorpholin-4-yl)-5-fluoropyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1COC(C)(C)CN1C(C(=C1)F)=NC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 WPLSNJRTQSTZGY-UHFFFAOYSA-N 0.000 claims description 3
- TZDULZPTEMCBGU-UHFFFAOYSA-N 6-[[2-[[6-(2,2-dimethylmorpholin-4-yl)-5-fluoropyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1COC(C)(C)CN1C(C(=C1)F)=NC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)COC3=CC=2)=N1 TZDULZPTEMCBGU-UHFFFAOYSA-N 0.000 claims description 3
- JPPONNNNUCFHBE-UHFFFAOYSA-N 6-[[2-[[6-(2,2-dimethylmorpholin-4-yl)-5-methylpyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound CC1=CC(NC=2N=C(NC=3N=C4NC(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=CN=C1N1CCOC(C)(C)C1 JPPONNNNUCFHBE-UHFFFAOYSA-N 0.000 claims description 3
- JCAPQQOYKKTCHV-UHFFFAOYSA-N 6-[[2-[[6-(2,2-dimethylmorpholin-4-yl)-5-methylpyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound CC1=CC(NC=2N=C(NC=3N=C4NC(=O)COC4=CC=3)C(F)=CN=2)=CN=C1N1CCOC(C)(C)C1 JCAPQQOYKKTCHV-UHFFFAOYSA-N 0.000 claims description 3
- AQIBZUFMVIUSCG-UHFFFAOYSA-N 6-[[2-[[6-(2,5-dimethylmorpholin-4-yl)pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound CC1COC(C)CN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)COC3=CC=2)=N1 AQIBZUFMVIUSCG-UHFFFAOYSA-N 0.000 claims description 3
- KLCGBJOXPZWFHE-UHFFFAOYSA-N 6-[[2-[[6-(4-ethoxypiperidin-1-yl)pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1CC(OCC)CCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 KLCGBJOXPZWFHE-UHFFFAOYSA-N 0.000 claims description 3
- PTJRUGNXIIIPLC-UHFFFAOYSA-N 6-[[2-[[6-(dimethylamino)pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1=NC(N(C)C)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 PTJRUGNXIIIPLC-UHFFFAOYSA-N 0.000 claims description 3
- VLKZSABFCITESO-OKILXGFUSA-N 6-[[2-[[6-[(2r,6s)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 VLKZSABFCITESO-OKILXGFUSA-N 0.000 claims description 3
- WZWGYXYCWPIQLX-OAHLLOKOSA-N 6-[[2-[[6-[(3r)-3-(ethylamino)pyrrolidin-1-yl]pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1[C@H](NCC)CCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 WZWGYXYCWPIQLX-OAHLLOKOSA-N 0.000 claims description 3
- YZEDMXPWRMYRRR-OAHLLOKOSA-N 6-[[2-[[6-[(3r)-3-ethoxypyrrolidin-1-yl]pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1[C@H](OCC)CCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 YZEDMXPWRMYRRR-OAHLLOKOSA-N 0.000 claims description 3
- GUVPOVFQVDZJSY-UHFFFAOYSA-N 6-[[2-[[6-[3-(diethylamino)pyrrolidin-1-yl]pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1C(N(CC)CC)CCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 GUVPOVFQVDZJSY-UHFFFAOYSA-N 0.000 claims description 3
- NCCBQCQDVCGDDD-UHFFFAOYSA-N 6-[[2-[[6-[3-(ethoxymethyl)morpholin-4-yl]pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound CCOCC1COCCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 NCCBQCQDVCGDDD-UHFFFAOYSA-N 0.000 claims description 3
- JDNSUONOYLDXHW-UHFFFAOYSA-N 6-[[2-[[6-[4-(diethylamino)piperidin-1-yl]pyridin-3-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1CC(N(CC)CC)CCN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 JDNSUONOYLDXHW-UHFFFAOYSA-N 0.000 claims description 3
- KLKDQWKIEQIVMX-UHFFFAOYSA-N 6-[[5-fluoro-2-[(5-fluoro-6-morpholin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=C1F)=CN=C1N1CCOCC1 KLKDQWKIEQIVMX-UHFFFAOYSA-N 0.000 claims description 3
- JSEPZRMEBFKSNP-UHFFFAOYSA-N 6-[[5-fluoro-2-[(5-fluoro-6-morpholin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C(NC=2N=C3NC(=O)COC3=CC=2)C(F)=CN=C1NC(C=C1F)=CN=C1N1CCOCC1 JSEPZRMEBFKSNP-UHFFFAOYSA-N 0.000 claims description 3
- HQQFUXDKUMFWJU-UHFFFAOYSA-N 6-[[5-fluoro-2-[(5-methoxy-6-morpholin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound COC1=CC(NC=2N=C(NC=3N=C4NC(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=CN=C1N1CCOCC1 HQQFUXDKUMFWJU-UHFFFAOYSA-N 0.000 claims description 3
- YGHLCQZDYAFXPK-UHFFFAOYSA-N 6-[[5-fluoro-2-[(5-methyl-6-morpholin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound CC1=CC(NC=2N=C(NC=3N=C4NC(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=CN=C1N1CCOCC1 YGHLCQZDYAFXPK-UHFFFAOYSA-N 0.000 claims description 3
- UURMTYJYGUUZKV-UHFFFAOYSA-N 6-[[5-fluoro-2-[(5-methyl-6-morpholin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound CC1=CC(NC=2N=C(NC=3N=C4NC(=O)COC4=CC=3)C(F)=CN=2)=CN=C1N1CCOCC1 UURMTYJYGUUZKV-UHFFFAOYSA-N 0.000 claims description 3
- IGLMOXQVWDIYHS-UHFFFAOYSA-N 6-[[5-fluoro-2-[(6-methylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1=NC(C)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)C(C)(C)OC3=CC=2)=N1 IGLMOXQVWDIYHS-UHFFFAOYSA-N 0.000 claims description 3
- WNIJAVTZKHTPCP-UHFFFAOYSA-N 6-[[5-fluoro-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCOCC1 WNIJAVTZKHTPCP-UHFFFAOYSA-N 0.000 claims description 3
- GEIZBFSXAAHZAR-UHFFFAOYSA-N 6-[[5-fluoro-2-[(6-pyridin-3-ylpyridin-3-yl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1C1=CC=CN=C1 GEIZBFSXAAHZAR-UHFFFAOYSA-N 0.000 claims description 3
- NPVRYCBJFSJIHV-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(1,4-oxazepan-4-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCCOCC1 NPVRYCBJFSJIHV-UHFFFAOYSA-N 0.000 claims description 3
- GFRNFHYHDKVXKS-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(2-oxo-1,3-oxazolidin-3-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCOC1=O GFRNFHYHDKVXKS-UHFFFAOYSA-N 0.000 claims description 3
- ZYCQBISJACHKPA-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(3-hydroxyazetidin-1-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CC(O)C1 ZYCQBISJACHKPA-UHFFFAOYSA-N 0.000 claims description 3
- XBWWMPFFBHDGTN-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(3-methylidenemorpholin-4-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCOCC1=C XBWWMPFFBHDGTN-UHFFFAOYSA-N 0.000 claims description 3
- SECGRXMXWOIZJZ-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(3-morpholin-4-ylpyrrolidin-1-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N(C1)CCC1N1CCOCC1 SECGRXMXWOIZJZ-UHFFFAOYSA-N 0.000 claims description 3
- ZVOZLRNNZQXGNZ-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(4-hydroxypiperidin-1-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCC(O)CC1 ZVOZLRNNZQXGNZ-UHFFFAOYSA-N 0.000 claims description 3
- OIYFGNOFQNMHKN-UHFFFAOYSA-N 6-[[5-fluoro-2-[[6-(4-morpholin-4-ylpiperidin-1-yl)pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N(CC1)CCC1N1CCOCC1 OIYFGNOFQNMHKN-UHFFFAOYSA-N 0.000 claims description 3
- WIMBWLBGQZNTQQ-KBPBESRZSA-N 6-[[5-fluoro-2-[[6-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1C(C)(C)C(=O)NC2=NC(NC=3C(F)=CN=C(N=3)NC3=CC=C(N=C3)N3C[C@]4(OC[C@]3([H])C4)[H])=CC=C21 WIMBWLBGQZNTQQ-KBPBESRZSA-N 0.000 claims description 3
- ZIWXRKMWNMTSAV-AWEZNQCLSA-N 6-[[5-fluoro-2-[[6-[(2r)-2-(fluoromethyl)morpholin-4-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound N1=C2NC(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)F)=NC=1NC(C=N1)=CC=C1N1CCO[C@@H](CF)C1 ZIWXRKMWNMTSAV-AWEZNQCLSA-N 0.000 claims description 3
- YVSXKHOYGWNIMK-GFCCVEGCSA-N 6-[[5-fluoro-2-[[6-[(2r)-2-methylmorpholin-4-yl]pyridin-3-yl]amino]pyrimidin-4-yl]amino]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound C1CO[C@H](C)CN1C(N=C1)=CC=C1NC1=NC=C(F)C(NC=2N=C3NC(=O)COC3=CC=2)=N1 YVSXKHOYGWNIMK-GFCCVEGCSA-N 0.000 claims description 3
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| PCT/US2011/032291 WO2011130390A1 (en) | 2010-04-13 | 2011-04-13 | 2, 4-pyrimidinediamine compounds and prodrugs thereof and their uses |
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| CA2792278C (en) * | 2010-04-13 | 2019-05-14 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and prodrugs thereof and their uses |
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| PT2736487T (pt) | 2011-07-28 | 2019-02-13 | Rigel Pharmaceuticals Inc | Novas formulações de (trimetoxifenilamino) pirimidinilo |
| WO2013020132A1 (en) * | 2011-08-04 | 2013-02-07 | The Brigham And Women's Hospital, Inc. | Methods of treating cardiovascular and metabolic diseases |
| ES2704744T3 (es) | 2012-06-13 | 2019-03-19 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| WO2013189241A1 (zh) * | 2012-06-20 | 2013-12-27 | 上海恒瑞医药有限公司 | 嘧啶二胺类衍生物、其制备方法及其在医药上的应用 |
| CN102746337B (zh) * | 2012-06-21 | 2014-12-17 | 成都苑东药业有限公司 | 一种2，4-嘧啶二胺类化合物及其制备方法 |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| MX361157B (es) * | 2012-08-30 | 2018-11-28 | Hoffmann La Roche | Compuestos inhibidores de pi3k de dioxino- y oxazin-[2,3-d]pirimid ina y métodos de uso. |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| US10130609B2 (en) | 2013-03-13 | 2018-11-20 | University Health Network | Pyrazole derivatives and their uses thereof |
| EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| FI3177281T3 (fi) * | 2014-08-08 | 2024-03-13 | Ali Res S R L | Rasvahappojen ja palmitoyylietanoliamidin seos käytettäväksi tulehduksellisten ja allergisten patologioiden hoitoon |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MX373169B (es) | 2015-02-20 | 2020-04-24 | Incyte Holdings Corp | Heterociclos bicíclicos como inhibidores de receptores del factor de crecimiento fibroblástico (fgfr). |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| MA52493A (fr) | 2018-05-04 | 2021-03-10 | Incyte Corp | Sels d'un inhibiteur de fgfr |
| CR20200590A (es) | 2018-05-04 | 2021-04-26 | Incyte Corp | Formas sólidas de un inhibidor de fgfr y procesos para prepararlas |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| TWI891666B (zh) | 2019-10-14 | 2025-08-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之雙環雜環 |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| BR112022010664A2 (pt) | 2019-12-04 | 2022-08-16 | Incyte Corp | Derivados de um inibidor de fgfr |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2022206797A1 (zh) * | 2021-03-30 | 2022-10-06 | 贝达药业股份有限公司 | Egfr抑制剂及其组合物和用途 |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含ｆｇｆｒ抑制劑及ｎｅｃｔｉｎ－４靶向劑之組合療法 |
| WO2022236255A2 (en) * | 2021-05-03 | 2022-11-10 | Nuvation Bio Inc. | Heterocyclic compounds as kinase inhibitors |
| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| EP4653444A1 (en) * | 2023-01-19 | 2025-11-26 | Hangzhou Innogate Pharma Co., Ltd. | Fused tricyclic compound as kinase inhibitor |
| CN119431398A (zh) * | 2023-07-31 | 2025-02-14 | 中国科学院上海有机化学研究所 | R406及其衍生物协同trail的抗肿瘤应用 |
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| US6573256B2 (en) | 1996-12-30 | 2003-06-03 | Bone Care International, Inc. | Method of inhibiting angiogenesis using active vitamin D analogues |
| FR2785284B1 (fr) | 1998-11-02 | 2000-12-01 | Galderma Res & Dev | Analogues de la vitamine d |
| US6358939B1 (en) | 1999-12-21 | 2002-03-19 | Northern Lights Pharmaceuticals, Llc | Use of biologically active vitamin D compounds for the prevention and treatment of inflammatory bowel disease |
| US6924400B2 (en) | 2001-12-10 | 2005-08-02 | Galderma Research & Development, Snc | Triaromatic vitamin D analogues |
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| US20070092888A1 (en) | 2003-09-23 | 2007-04-26 | Cornelius Diamond | Diagnostic markers of hypertension and methods of use thereof |
| EP1814878B1 (en) * | 2004-11-24 | 2012-01-04 | Rigel Pharmaceuticals, Inc. | Spiro-2, 4-pyrimidinediamine compounds and their uses |
| DE602006010979D1 (de) * | 2005-01-19 | 2010-01-21 | Rigel Pharmaceuticals Inc | Prodrugs aus 2,4-pyrimidindiamin-verbindungen und ihre verwendungen |
| US8227455B2 (en) | 2005-04-18 | 2012-07-24 | Rigel Pharmaceuticals, Inc. | Methods of treating cell proliferative disorders |
| US7713987B2 (en) | 2005-12-06 | 2010-05-11 | Rigel Pharmaceuticals, Inc. | Pyrimidine-2,4-diamines and their uses |
| EP2420505A1 (en) | 2006-11-21 | 2012-02-22 | Rigel Pharmaceuticals, Inc. | Prodrug salts of 2, 4- pyrimidinediamine compounds and their uses |
| WO2008118823A2 (en) | 2007-03-26 | 2008-10-02 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US20090012045A1 (en) * | 2007-06-26 | 2009-01-08 | Rigel Pharmaceuticals, Inc. | Methods of Treating Cell Proliferative Disorders |
| TWI546290B (zh) * | 2008-06-27 | 2016-08-21 | 賽基艾維洛米斯研究股份有限公司 | 雜芳基化合物及其用途 |
| ES2542884T3 (es) * | 2008-09-23 | 2015-08-12 | Rigel Pharmaceuticals, Inc. | Inhibidores de JAK de carbamato tricíclico |
| ES2624622T3 (es) | 2008-12-30 | 2017-07-17 | Rigel Pharmaceuticals, Inc. | Inhibidores de pirimidindiamina cinasa |
| ES2524127T3 (es) | 2009-11-20 | 2014-12-04 | Rigel Pharmaceuticals, Inc. | Compuestos de 2,4-pirimidinodiamina y sus profármacos y sus usos |
| CA2792278C (en) * | 2010-04-13 | 2019-05-14 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and prodrugs thereof and their uses |
-
2011
- 2011-04-13 CA CA2792278A patent/CA2792278C/en active Active
- 2011-04-13 WO PCT/US2011/032291 patent/WO2011130390A1/en not_active Ceased
- 2011-04-13 US US13/086,081 patent/US8618095B2/en active Active
- 2011-04-13 EP EP11730116.8A patent/EP2558474B1/en active Active
- 2011-04-13 ES ES11730116.8T patent/ES2562419T3/es active Active
- 2011-04-13 JP JP2013505087A patent/JP6067550B2/ja active Active
-
2015
- 2015-09-30 JP JP2015193022A patent/JP2016041700A/ja active Pending
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