JP2012503604A5 - - Google Patents
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- JP2012503604A5 JP2012503604A5 JP2011528087A JP2011528087A JP2012503604A5 JP 2012503604 A5 JP2012503604 A5 JP 2012503604A5 JP 2011528087 A JP2011528087 A JP 2011528087A JP 2011528087 A JP2011528087 A JP 2011528087A JP 2012503604 A5 JP2012503604 A5 JP 2012503604A5
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- pyrimidinediamine
- indeno
- tetrahydro
- methyl
- 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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- 150000001875 compounds Chemical class 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- -1 amino, substituted amino, carboxyl Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 102000042838 JAK family Human genes 0.000 claims description 14
- 108091082332 JAK family Proteins 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 8
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
- NTTGYQKAKHVMNF-MOPGFXCFSA-N (3ar,8bs)-7-[[4-(2,3-dihydro-1,4-benzodioxin-5-ylamino)-5-methylpyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound O1CCOC2=C1C=CC=C2NC1=NC(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)=NC=C1C NTTGYQKAKHVMNF-MOPGFXCFSA-N 0.000 claims description 2
- UVJVCQQMPSMBQV-UXHICEINSA-N (3ar,8bs)-7-[[4-[(2,2-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)amino]-5-methylpyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound O1C(C)(C)C(=O)NC2=CC(NC3=NC(NC=4C=C5[C@@H]6NC(=O)O[C@@H]6CC5=CC=4)=NC=C3C)=CC=C21 UVJVCQQMPSMBQV-UXHICEINSA-N 0.000 claims description 2
- HIDWGGVLNMQJDI-YADHBBJMSA-N (3ar,8bs)-7-[[4-[(4-ethyl-2,2-dimethyl-3-oxo-1,4-benzoxazin-6-yl)amino]-5-methylpyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(CC)C(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)C)=NC=1NC(C=C12)=CC=C1C[C@@H]1[C@H]2NC(=O)O1 HIDWGGVLNMQJDI-YADHBBJMSA-N 0.000 claims description 2
- YXGLPMBFALCHJM-MSOLQXFVSA-N (3ar,8bs)-7-[[5-chloro-4-(2,3-dihydro-1,4-benzodioxin-5-ylamino)pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound O1CCOC2=C1C=CC=C2NC1=NC(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)=NC=C1Cl YXGLPMBFALCHJM-MSOLQXFVSA-N 0.000 claims description 2
- DFSHLWOLFJGTEN-YAQHWNNOSA-N (3ar,8bs)-7-[[5-chloro-4-(2,3-dihydro-1h-inden-4-ylamino)-5-methyl-4h-pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1(Cl)C=NC(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)=NC1NC1=CC=CC2=C1CCC2 DFSHLWOLFJGTEN-YAQHWNNOSA-N 0.000 claims description 2
- GNBCSICJCDWIIX-RTWAWAEBSA-N (3ar,8bs)-7-[[5-chloro-4-(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1CCCC2=C1C=CC=C2NC1=NC(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)=NC=C1Cl GNBCSICJCDWIIX-RTWAWAEBSA-N 0.000 claims description 2
- POOVTNBASOLYTF-UXHICEINSA-N (3ar,8bs)-7-[[5-chloro-4-[(2,2,4-trimethyl-3-oxo-1,4-benzoxazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(C)C(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)Cl)=NC=1NC(C=C12)=CC=C1C[C@@H]1[C@H]2NC(=O)O1 POOVTNBASOLYTF-UXHICEINSA-N 0.000 claims description 2
- QBUTXIWMTYTWAG-CVEARBPZSA-N (3ar,8bs)-7-[[5-chloro-4-[(2,2-difluoro-1,3-benzodioxol-4-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C=12OC(F)(F)OC2=CC=CC=1NC(C(=CN=1)Cl)=NC=1NC(C=C12)=CC=C1C[C@@H]1[C@H]2NC(=O)O1 QBUTXIWMTYTWAG-CVEARBPZSA-N 0.000 claims description 2
- QHNRSODSZAPMJQ-RTWAWAEBSA-N (3ar,8bs)-7-[[5-chloro-4-[(4-ethyl-2,2-dimethyl-3-oxo-1,4-benzoxazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(CC)C(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)Cl)=NC=1NC(C=C12)=CC=C1C[C@@H]1[C@H]2NC(=O)O1 QHNRSODSZAPMJQ-RTWAWAEBSA-N 0.000 claims description 2
- LRYHYBJLHRJMRV-RPWUZVMVSA-N (3ar,8bs)-7-[[5-fluoro-4-[4-(2-pyridin-4-ylethyl)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound FC1=CN=C(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1CCC1=CC=NC=C1 LRYHYBJLHRJMRV-RPWUZVMVSA-N 0.000 claims description 2
- WJNZUEHGXCVNMT-PKTZIBPZSA-N (3ar,8bs)-7-[[5-fluoro-4-[4-(pyridin-2-ylmethoxy)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound FC1=CN=C(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1OCC1=CC=CC=N1 WJNZUEHGXCVNMT-PKTZIBPZSA-N 0.000 claims description 2
- ILZRWQGBCDRMTM-YADHBBJMSA-N (3ar,8bs)-7-[[5-methyl-4-(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1CCCC2=C1C=CC=C2NC1=NC(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)=NC=C1C ILZRWQGBCDRMTM-YADHBBJMSA-N 0.000 claims description 2
- QDEZKIPXCZIJQK-RTWAWAEBSA-N (3ar,8bs)-7-[[5-methyl-4-[(2,2,4-trimethyl-3-oxo-1,4-benzoxazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(C)C(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)C)=NC=1NC(C=C12)=CC=C1C[C@@H]1[C@H]2NC(=O)O1 QDEZKIPXCZIJQK-RTWAWAEBSA-N 0.000 claims description 2
- LFXYNDJMAWSNCO-RPWUZVMVSA-N (3ar,8bs)-7-[[5-methyl-4-[4-(pyridin-2-ylmethoxy)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1=CN=C(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1OCC1=CC=CC=N1 LFXYNDJMAWSNCO-RPWUZVMVSA-N 0.000 claims description 2
- JJFVYFFGUVGGBG-RPWUZVMVSA-N (3ar,8bs)-7-[[5-methyl-4-[4-(pyridin-3-ylmethoxy)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1=CN=C(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1OCC1=CC=CN=C1 JJFVYFFGUVGGBG-RPWUZVMVSA-N 0.000 claims description 2
- UVJVCQQMPSMBQV-VQTJNVASSA-N (3as,8br)-7-[[4-[(2,2-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)amino]-5-methylpyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound O1C(C)(C)C(=O)NC2=CC(NC3=NC(NC=4C=C5[C@H]6NC(=O)O[C@H]6CC5=CC=4)=NC=C3C)=CC=C21 UVJVCQQMPSMBQV-VQTJNVASSA-N 0.000 claims description 2
- DFSHLWOLFJGTEN-OHJIBLAUSA-N (3as,8br)-7-[[5-chloro-4-(2,3-dihydro-1h-inden-4-ylamino)-5-methyl-4h-pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1(Cl)C=NC(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)=NC1NC1=CC=CC2=C1CCC2 DFSHLWOLFJGTEN-OHJIBLAUSA-N 0.000 claims description 2
- GNBCSICJCDWIIX-LEWJYISDSA-N (3as,8br)-7-[[5-chloro-4-(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1CCCC2=C1C=CC=C2NC1=NC(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)=NC=C1Cl GNBCSICJCDWIIX-LEWJYISDSA-N 0.000 claims description 2
- LRYHYBJLHRJMRV-BJKOFHAPSA-N (3as,8br)-7-[[5-fluoro-4-[4-(2-pyridin-4-ylethyl)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound FC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1CCC1=CC=NC=C1 LRYHYBJLHRJMRV-BJKOFHAPSA-N 0.000 claims description 2
- WJNZUEHGXCVNMT-XZOQPEGZSA-N (3as,8br)-7-[[5-fluoro-4-[4-(pyridin-2-ylmethoxy)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound FC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1OCC1=CC=CC=N1 WJNZUEHGXCVNMT-XZOQPEGZSA-N 0.000 claims description 2
- ILZRWQGBCDRMTM-FCHUYYIVSA-N (3as,8br)-7-[[5-methyl-4-(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1CCCC2=C1C=CC=C2NC1=NC(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)=NC=C1C ILZRWQGBCDRMTM-FCHUYYIVSA-N 0.000 claims description 2
- NJTKZLTXMRVMMV-PZJWPPBQSA-N (3as,8br)-7-[[5-methyl-4-[(2,2,4-trimethyl-3-oxo-1,4-benzothiazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(C)C(=O)C(C)(C)SC2=CC=C1NC(C(=CN=1)C)=NC=1NC(C=C12)=CC=C1C[C@H]1[C@@H]2NC(=O)O1 NJTKZLTXMRVMMV-PZJWPPBQSA-N 0.000 claims description 2
- QDEZKIPXCZIJQK-LEWJYISDSA-N (3as,8br)-7-[[5-methyl-4-[(2,2,4-trimethyl-3-oxo-1,4-benzoxazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(C)C(=O)C(C)(C)OC2=CC=C1NC(C(=CN=1)C)=NC=1NC(C=C12)=CC=C1C[C@H]1[C@@H]2NC(=O)O1 QDEZKIPXCZIJQK-LEWJYISDSA-N 0.000 claims description 2
- MFSOEJLIHCETIT-JTHBVZDNSA-N (3as,8br)-7-[[5-methyl-4-[(3-oxo-4-propyl-1,4-benzoxazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(CCC)C(=O)COC2=CC=C1NC(C(=CN=1)C)=NC=1NC(C=C12)=CC=C1C[C@H]1[C@@H]2NC(=O)O1 MFSOEJLIHCETIT-JTHBVZDNSA-N 0.000 claims description 2
- MIOFWJOSEYOEBR-GHTZIAJQSA-N (3as,8br)-7-[[5-methyl-4-[(4-methyl-3-oxo-1,4-benzothiazin-6-yl)amino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound C1=C2N(C)C(=O)CSC2=CC=C1NC(C(=CN=1)C)=NC=1NC(C=C12)=CC=C1C[C@H]1[C@@H]2NC(=O)O1 MIOFWJOSEYOEBR-GHTZIAJQSA-N 0.000 claims description 2
- LFXYNDJMAWSNCO-BJKOFHAPSA-N (3as,8br)-7-[[5-methyl-4-[4-(pyridin-2-ylmethoxy)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1OCC1=CC=CC=N1 LFXYNDJMAWSNCO-BJKOFHAPSA-N 0.000 claims description 2
- JJFVYFFGUVGGBG-BJKOFHAPSA-N (3as,8br)-7-[[5-methyl-4-[4-(pyridin-3-ylmethoxy)anilino]pyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1OCC1=CC=CN=C1 JJFVYFFGUVGGBG-BJKOFHAPSA-N 0.000 claims description 2
- ZRGUAWDZNKYUTB-UXHICEINSA-N 3-[[2-[[(3ar,8bs)-2-oxo-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-7-yl]amino]-5-chloropyrimidin-4-yl]amino]-n-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=CC(NC=2C(=CN=C(NC=3C=C4[C@@H]5NC(=O)O[C@@H]5CC4=CC=3)N=2)Cl)=C1 ZRGUAWDZNKYUTB-UXHICEINSA-N 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000032027 Essential Thrombocythemia Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 208000017733 acquired polycythemia vera Diseases 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 238000010322 bone marrow transplantation Methods 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 206010028537 myelofibrosis Diseases 0.000 claims description 2
- YZIAXLQCWQGICF-FCHUYYIVSA-N n-[2-[4-[[2-[[(3as,8br)-2-oxo-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-7-yl]amino]-5-chloropyrimidin-4-yl]amino]phenyl]ethyl]cyclopropanesulfonamide Chemical compound ClC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1CCNS(=O)(=O)C1CC1 YZIAXLQCWQGICF-FCHUYYIVSA-N 0.000 claims description 2
- ZAXFOQPUHRVKIE-YADHBBJMSA-N n-[[4-[[2-[[(3ar,8bs)-2-oxo-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-7-yl]amino]-5-chloropyrimidin-4-yl]amino]-3-methylphenyl]methyl]cyclopropanesulfonamide Chemical compound C=1C=C(NC=2C(=CN=C(NC=3C=C4[C@@H]5NC(=O)O[C@@H]5CC4=CC=3)N=2)Cl)C(C)=CC=1CNS(=O)(=O)C1CC1 ZAXFOQPUHRVKIE-YADHBBJMSA-N 0.000 claims description 2
- LUAGQDDETFUDIS-RTWAWAEBSA-N n-[[4-[[2-[[(3ar,8bs)-2-oxo-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-7-yl]amino]-5-chloropyrimidin-4-yl]amino]phenyl]methyl]cyclopropanesulfonamide Chemical compound ClC1=CN=C(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1CNS(=O)(=O)C1CC1 LUAGQDDETFUDIS-RTWAWAEBSA-N 0.000 claims description 2
- MYIINNCGIMSNAP-YADHBBJMSA-N n-[[4-[[2-[[(3ar,8bs)-2-oxo-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-7-yl]amino]-5-methylpyrimidin-4-yl]amino]phenyl]methyl]cyclopropanesulfonamide Chemical compound CC1=CN=C(NC=2C=C3[C@@H]4NC(=O)O[C@@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1CNS(=O)(=O)C1CC1 MYIINNCGIMSNAP-YADHBBJMSA-N 0.000 claims description 2
- LUAGQDDETFUDIS-LEWJYISDSA-N n-[[4-[[2-[[(3as,8br)-2-oxo-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-7-yl]amino]-5-chloropyrimidin-4-yl]amino]phenyl]methyl]cyclopropanesulfonamide Chemical compound ClC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC(C=C1)=CC=C1CNS(=O)(=O)C1CC1 LUAGQDDETFUDIS-LEWJYISDSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 208000037244 polycythemia vera Diseases 0.000 claims description 2
- 208000003476 primary myelofibrosis Diseases 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000005338 substituted cycloalkoxy group Chemical group 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
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- OADCDRCRKFPSHZ-LEWJYISDSA-N (3as,8br)-7-[[4-(2,3-dihydro-1h-inden-4-ylamino)-5-methylpyrimidin-2-yl]amino]-1,3a,4,8b-tetrahydroindeno[1,2-d][1,3]oxazol-2-one Chemical compound CC1=CN=C(NC=2C=C3[C@H]4NC(=O)O[C@H]4CC3=CC=2)N=C1NC1=CC=CC2=C1CCC2 OADCDRCRKFPSHZ-LEWJYISDSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
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| US9950708P | 2008-09-23 | 2008-09-23 | |
| US61/099,507 | 2008-09-23 | ||
| PCT/US2009/057972 WO2010039518A2 (en) | 2008-09-23 | 2009-09-23 | Tricyclic carbamate jak inhibitors |
Publications (3)
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| JP2012503604A JP2012503604A (ja) | 2012-02-09 |
| JP2012503604A5 true JP2012503604A5 (https=) | 2013-05-30 |
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| EP (1) | EP2344476B1 (https=) |
| JP (1) | JP5518076B2 (https=) |
| CA (1) | CA2736258C (https=) |
| ES (1) | ES2542884T3 (https=) |
| WO (1) | WO2010039518A2 (https=) |
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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 |
| US20160123982A1 (en) | 2013-02-04 | 2016-05-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for assaying jak2 activity in red blood cells and uses thereof |
| WO2015019365A1 (en) | 2013-08-07 | 2015-02-12 | Cadila Healthcare Limited | N-cyanomethylamides as inhibitors of janus kinase |
| WO2018167283A1 (en) | 2017-03-17 | 2018-09-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma associated neural remodeling |
| EP3610264A1 (en) | 2017-04-13 | 2020-02-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma |
| WO2020092015A1 (en) | 2018-11-02 | 2020-05-07 | University Of Rochester | Therapeutic mitigation of epithelial infection |
| CA3128521A1 (en) * | 2019-02-27 | 2020-09-03 | Millennium Pharmaceuticals, Inc. | Administration of sumo-activating enzyme inhibitor and checkpoint inhibitors |
| US20220372135A1 (en) | 2019-09-27 | 2022-11-24 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| US11691971B2 (en) | 2020-06-19 | 2023-07-04 | Incyte Corporation | Naphthyridinone compounds as JAK2 V617F inhibitors |
| WO2021257863A1 (en) | 2020-06-19 | 2021-12-23 | Incyte Corporation | Pyrrolotriazine compounds as jak2 v617f inhibitors |
| CR20230057A (es) | 2020-07-02 | 2023-08-15 | Incyte Corp | Compuestos tríciclicos de urea como inhibidores de jak2 v617f |
| US11767323B2 (en) | 2020-07-02 | 2023-09-26 | Incyte Corporation | Tricyclic pyridone compounds as JAK2 V617F inhibitors |
| US11661422B2 (en) | 2020-08-27 | 2023-05-30 | Incyte Corporation | Tricyclic urea compounds as JAK2 V617F inhibitors |
| US11919908B2 (en) | 2020-12-21 | 2024-03-05 | Incyte Corporation | Substituted pyrrolo[2,3-d]pyrimidine compounds as JAK2 V617F inhibitors |
| AR125273A1 (es) | 2021-02-25 | 2023-07-05 | Incyte Corp | Lactamas espirocíclicas como inhibidores de jak2 v617f |
| AU2023235313A1 (en) | 2022-03-17 | 2024-10-03 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| 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 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| HRP20050089B1 (hr) * | 2002-07-29 | 2015-06-19 | Rigel Pharmaceuticals | Upotreba 2,4 pirimidindiaminskog spoja za proizvodnju lijeka za lijeäśenje ili sprjeäśavanje autoimunosne bolesti |
| EP1883302A4 (en) * | 2005-05-03 | 2009-05-20 | Rigel Pharmaceuticals Inc | JAK KINASE HEMMER AND ITS USE |
| BRPI0610876B8 (pt) * | 2005-06-08 | 2021-05-25 | Rigel Pharmaceuticals Inc | composto, formulação farmacêutica, e métodos de inibir uma atividade de uma jak cinase, e de inibir uma cascata de transdução de sinal em que jak3 cinase desempenha um papel |
| ES2622493T3 (es) * | 2006-02-24 | 2017-07-06 | Rigel Pharmaceuticals, Inc. | Composiciones y métodos para la inhibición de la ruta de JAK |
| JP5161233B2 (ja) * | 2006-10-19 | 2013-03-13 | ライジェル ファーマシューティカルズ， インコーポレイテッド | 自己免疫疾患の処置のためのｊａｋキナーゼの阻害剤としての２，４−ピリミジンアミン誘導体 |
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2009
- 2009-09-23 ES ES09818261.1T patent/ES2542884T3/es active Active
- 2009-09-23 EP EP20090818261 patent/EP2344476B1/en not_active Not-in-force
- 2009-09-23 JP JP2011528087A patent/JP5518076B2/ja not_active Expired - Fee Related
- 2009-09-23 WO PCT/US2009/057972 patent/WO2010039518A2/en not_active Ceased
- 2009-09-23 CA CA2736258A patent/CA2736258C/en active Active
- 2009-09-23 US US13/119,950 patent/US8846908B2/en active Active
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2014
- 2014-08-22 US US14/466,697 patent/US20140363443A1/en not_active Abandoned
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