JP2014510789A5 - - Google Patents

Info

Publication number

JP2014510789A5

JP2014510789A5 JP2014505254A JP2014505254A JP2014510789A5 JP 2014510789 A5 JP2014510789 A5 JP 2014510789A5 JP 2014505254 A JP2014505254 A JP 2014505254A JP 2014505254 A JP2014505254 A JP 2014505254A JP 2014510789 A5 JP2014510789 A5 JP 2014510789A5

Authority

JP

Japan

Prior art keywords

jak1

inhibitor

composition

immunosuppressive agent

inhibitory

Prior art date

2012-04-11

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

Links

• Espacenet
• Global Dossier
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• 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 claims description 89
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 89
• 230000002401 inhibitory effect Effects 0.000 claims description 55
• 239000003112 inhibitor Substances 0.000 claims description 52
• 239000003018 immunosuppressive agent Substances 0.000 claims description 51
• 229940125721 immunosuppressive agent Drugs 0.000 claims description 42
• 239000000203 mixture Substances 0.000 claims description 39
• 229940122739 Calcineurin inhibitor Drugs 0.000 claims description 18
• 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 claims description 18
• 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 claims description 18
• 150000001875 compounds Chemical class 0.000 claims description 14
• 229940002612 prodrug Drugs 0.000 claims description 14
• 239000000651 prodrug Substances 0.000 claims description 14
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 13
• 229960001967 tacrolimus Drugs 0.000 claims description 13
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims description 13
• 230000002301 combined effect Effects 0.000 claims description 12
• 229960003444 immunosuppressant agent Drugs 0.000 claims description 9
• 230000001861 immunosuppressant effect Effects 0.000 claims description 7
• ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 claims description 6
• 230000000694 effects Effects 0.000 claims description 6
• 210000000056 organ Anatomy 0.000 claims description 6
• -1 2- (4-Fluoro-3-methoxy-5-methylphenylamino) -5-methylpyrimidin-4-ylamino Chemical group 0.000 claims description 5
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 5
• 108010036949 Cyclosporine Proteins 0.000 claims description 5
• 229960001265 ciclosporin Drugs 0.000 claims description 5
• 229930182912 cyclosporin Natural products 0.000 claims description 5
• KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 claims description 5
• 229960005330 pimecrolimus Drugs 0.000 claims description 5
• OYFMQDVLFYKOPZ-UHFFFAOYSA-N 5-[[2-(4-fluoro-3-methoxy-5-methylanilino)-5-methylpyrimidin-4-yl]amino]-3h-1,3-benzoxazol-2-one Chemical compound CC1=C(F)C(OC)=CC(NC=2N=C(NC=3C=C4NC(=O)OC4=CC=3)C(C)=CN=2)=C1 OYFMQDVLFYKOPZ-UHFFFAOYSA-N 0.000 claims description 4
• 230000002195 synergetic effect Effects 0.000 claims description 4
• HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 3
• 101710088194 Dehydrogenase Proteins 0.000 claims description 3
• GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 claims description 3
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 3
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• MBTOOKBKBYXTCE-UHFFFAOYSA-L disodium;methyl phosphate Chemical compound [Na+].[Na+].COP([O-])([O-])=O MBTOOKBKBYXTCE-UHFFFAOYSA-L 0.000 claims description 3
• 235000013902 inosinic acid Nutrition 0.000 claims description 3
• 210000003734 kidney Anatomy 0.000 claims description 3
• 210000004185 liver Anatomy 0.000 claims description 3
• 210000004072 lung Anatomy 0.000 claims description 3
• 230000003247 decreasing effect Effects 0.000 description 4
• 230000036039 immunity Effects 0.000 description 2