CN101925572A - 二氢化茚酰胺化合物制备方法、包含其的药物组合物、及其作为蛋白激酶抑制的应用 - Google Patents
二氢化茚酰胺化合物制备方法、包含其的药物组合物、及其作为蛋白激酶抑制的应用 Download PDFInfo
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- CN101925572A CN101925572A CN2009801031146A CN200980103114A CN101925572A CN 101925572 A CN101925572 A CN 101925572A CN 2009801031146 A CN2009801031146 A CN 2009801031146A CN 200980103114 A CN200980103114 A CN 200980103114A CN 101925572 A CN101925572 A CN 101925572A
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- C07D403/14—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 three or more hetero rings
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Abstract
Description
Claims (17)
- 权 利 一种由下面通式 I表示的化合物:式 I或药学上可接受的盐或其前药, 其中:R1是一个饱和环状氨基, 可选地被 1, 2, 3, 或 4个 Rla取代;Rla是氢原子, 卤素, 氨基, Cw烷基, Cw羟烷基, Cw卤代烷基, Ci-6 氰代烷基, ORa , SRa , RbRc , RbC(0)Rd , NRbS(0)2Rd , C(0) RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C2-6烯基, C2-6炔基, 芳基, 杂芳 基, 环烷基, 或杂环烷基, 其中所述的 C1-6烷基, C2-6烯基, C2-6炔基, 芳 基, 杂芳基, 环烷基, 和杂环烷基可选地被 1, 2, 或 3个独立选自于氨基, 卤素, ORa , SRa , RbRc , Rb(CO)Rd , RbS(0)2Rd , C(0) RbRc , S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C1-6卤代烷基, C1-6羟烷基, C1-6 氰代烷基, 芳基, 杂芳基, 环烷基, 和杂环烷基的基团所取代;或者两个 Rla基团和同它们连接的原子一起形成一个 3, 4, 5, 6或 7 元环的环烷基或杂环烷基, 并可选地被 1, 2, 或 3个独立选自于氨基, 卤素, ORa, SRa, RbRc, Rb(CO)Rd, RbS(0)2Rd, C(0) RbRc, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C1-6卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6 婦基, C2_6炔基, 芳基, 杂芳基, 环烷基, 和杂环烷基的基团所取代;R2是氢原子, 卤素, 氨基, ORa, SRa, RbRc, Cw烷基, Cw羟烷 基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基;或者两个 R2基团与和它们连接的原子一起形成 3, 4, 5, 6, 或 7元环 的环烷基或杂环烷基, 并可选地被 1, 2, 或 3 个独立选自于氨基, 卤素, ORa, SRa, RbRc, Rb(CO)Rd, RbS(0)2Rd, C(0) RbRc, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C1-6 1¾代烷基, C1-6羟烷基, C1-6氰代烷基,C2-6婦基, 和 C2.6炔基的基团所取代; R3是氢原子, 卤素, 氰基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, 环烷基, 或杂环烷基; 或者两个 R3基团与和它们连接的原子一起形成一个 5 , 6, 或 7元环的 环烷基或杂环烷基, 并可选地被 1 , 2, 或 3个独立选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯 基, 和 C2_6炔基的基团所取代;W-X是一个酰胺键;Y是一个杂芳基, 可选地被 1 , 2, 或 3个 R4所取代;Z是一个杂环烷基, 或杂芳基, 可选地被 1 , 2, 或 3个 R5所取代;R4和 R5独立地选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6 羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, Rb(CO)Rd, C(0) RbRc, RbS(0)2Rd, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, 环烷 基, 杂环烷基, 芳基, 和杂芳基或者两个 R4基团或两个 R5基团各自与同它们连接的原子形成一个 5 , 6, 或 7元环的环烷基或杂环烷基, 并可选地被 1 , 2, 或 3个独立选自于卤 素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, C1-6 氰代烷基, C2.6烯基, 和 C2.6炔基的基团所取代;Ra, Rb, Rc, 和 Rd独立地选自于氢原子, C1-6烷基, C1-6卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, 环烷基, 杂环烷基, 芳基, 和杂芳基;或者 1^和1^与同它们连接的氮原子一起形成 4, 5 , 6, 或 7元环的杂 环烷基, 并可选地被 1 , 2, 或 3个独立选自于卤素, 氨基, Cw烷基, Ci-6 卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, 和 C2-6炔基, 环烷基, 杂 环烷基, 芳基, 和杂芳基的基团所取代;n是一个从 0到 4的整数;m是一个从 0到 2的整数。2. 根据权利要求 1所述的化合物或药学上可接受的盐或其前药, 具有通式 II:式 II其中, R1如在权利要求 1中所定义。3. 根据权利要求 1或 2所述的化合物或药学上可接受的盐或其前药, 其中:R1是一个饱和环状氨基, 选自于哌啶基, 哌嗪基, 吡咯烷基, 氮杂环 丁烷基, 和吗啉基, 每个基团可选地被 1, 2, 3, 或 4个 Rla取代;Rla是氢原子, 卤素, 氨基, Cw烷基, Cw羟烷基, Cw卤代烷基, Ci-6 氰代烷基, ORa , SRa , RbRc , RbC(0)Rd , NRbS(0)2Rd , C(0) RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C2-6烯基, 。2-6炔基, 芳基, 杂芳 基, 环烷基, 或杂环烷基, 其中所述的 C1-6烷基, C2-6烯基, C2-6炔基, 芳 基, 杂芳基, 环烷基, 和杂环烷基可选地被 1, 2, 或 3个独立选自于氨基, 卤素, ORa , SRa , RbRc , Rb(CO)Rd , RbS(0)2Rd , C(0) RbRc , S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C1-6卤代烷基, C1-6羟烷基, C1-6 氰代烷基, 芳基, 杂芳基, 环烷基, 和杂环烷基的基团所取代;或者两个 Rla基团和同它们连接的原子一起形成一个 3, 4, 5, 6或 7 元环的环烷基或杂环烷基, 并可选地被 1, 2, 或 3个独立选自于氨基, 卤素, ORa, SRa, RbRc, Rb(CO)Rd, RbS(0)2Rd, C(0) RbRc, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C1-6卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6 婦基, C2_6炔基, 芳基, 杂芳基, 环烷基, 和杂环烷基的基团所取代;Y选自于吡啶基, 嘧啶基, 哒嗪基, 吡嗪基, 三嗪基, 噻唑基, 异噻 唑基, 咪唑基, 噁唑基, 异噁峻基, 三唑基, 或吡峻基, 并可选地被 1, 2, 或 3个 R4所取代;Z选自于吡啶基, 嘧啶基, 哒嗪基, 吡嗪基, 三嗪基, 噻唑基, 异噻唑 基, 咪唑基, 噁唑基, 异噁峻基, 三唑基, 吡峻基, 氮噁峻基, 吡咯并吡啶 基, 吡咯并嘧啶基, 吡唑并吡啶基, 吡唑并嘧啶基, 喹啉基, 异喹啉基, 喹 唑啉基, 哌嗪基, 或吗啉基, 并可选地被 1, 2, 或 3个 R5所取代;R4和 R5独立地选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6 羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, Rb(CO)Rd, C(0) RbRc, RbS(0)2Rd, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, 环烷 基, 杂环烷基, 芳基, 和杂芳基;或者两个 R4基团或两个 R5基团各自与同它们连接的原子一起形成一 个 5 , 6, 或 7元环的环烷基或杂环烷基, 并可选地被 1 , 2, 或 3个独立选自 于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, d.6氰代烷基, C2.6婦基, 和 C2.6炔基的基团所取代;Ra, Rb, Rc, 和 Rd独立地选自于氢原子, C1-6烷基, C1-6卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, 环烷基, 杂环烷基, 芳基, 和杂芳基;或者 1^和1^与同它们连接的氮原子一起形成 4, 5 , 6, 或 7元环的杂 环烷基, 并可选地被 1 , 2, 或 3个独立选自于卤素, 氨基, Cw烷基, Ci-6 卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, 和 C2-6炔基, 环烷基, 杂 环烷基, 芳基, 和杂芳基的基团所取代。4. 根据权利要求 1-3任一项所述的化合物或药学上可接受的盐或其前药, 具有 通式 Ila:式 Ila其巾:R6和 R7独立地选自于氢原子, 氨基, C1-6烷基, C1-6羟烷基, C1-6卤代 烷基, C1-6氰代烷基, 。2-6烯基, C2-6炔基;或者 R6和 R7与同它们连接的原子一起形成一个 5 , 6, 或 7元环的碳 环或杂环, 并可选地被 1 , 2, 或 3 个独立选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, 和C2_6炔基的基团所取代;R8是氢原子, Cw烷基, Cw羟烷基, Cw卤代烷基, Cw氰代烷基,C(0) RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C3-6烯基, C3-6炔基, 芳基, 杂芳 基, 环烷基, 和杂环烷基, 其中所述的 C1-6烷基, C3-6烯基, C3-6炔基, 芳基, 杂芳基, 环烷基, 和杂环烷基可选地被 1 , 2, 或 3个独立选自于卤素, 氨基, ORa, SRa, RbR 基团所取代;Y选自于吡啶基, 嘧啶基, 哒嗪基, 吡嗪基, 三嗪基, 噻唑基, 异噻 唑基, 咪唑基, 噁唑基, 异噁峻基, 三唑基, 或吡峻基, 并可选地被 1 , 2, 或 3个 R4所取代;Z选自于吡啶基, 嘧啶基, 哒嗪基, 吡嗪基, 三嗪基, 噻唑基, 异噻唑 基, 咪唑基, 噁唑基, 异噁峻基, 三唑基, 吡峻基, 氮噁峻基, 吡咯并吡啶 基, 吡咯并嘧啶基, 吡唑并吡啶基, 吡唑并嘧啶基, 喹啉基, 异喹啉基, 喹 唑啉基, 哌嗪基, 或吗啉基, 并可选地被 1 , 2, 或 3个 R5所取代;R4和 R5独立地选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6 羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, Rb(CO)Rd, C(0) RbRc, RbS(0)2Rd, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, 环烷 基, 杂环烷基, 芳基, 和杂芳基;或者两个 R4基团或两个 R5基团各自与同它们连接的原子一起形成一 个 5 , 6, 或 7元环的环烷基或杂环烷基, 并可选地被 1 , 2, 或 3个独立选自 于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, d.6氰代烷基, C2.6烯基, 和 C2.6炔基的基团所取代;Ra, Rb, Rc, 和 Rd独立地选自于氢原子, C1-6烷基, C1-6卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, 环烷基, 杂环烷基, 芳基, 和杂芳基;或者 1^和1^与同它们连接的氮原子一起形成 4, 5 , 6, 或 7元环的杂 环烷基, 并可选地被 1 , 2, 或 3个独立选自于卤素, 氨基, Cw烷基, Ci-6 卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, 和 C2-6炔基, 环烷基, 杂 环烷基, 芳基, 和杂芳基的基团所取代;p是一个从 1到 2的整数。 根据权利要求 1-3任一项所述的化合物或药学上可接受的盐或其前药, 具有 通式 lib:式 lib其巾:R9和 R1Q独立地选自于氢原子, C1-6烷基, C2-6羟烷基, C2-6卤代烷基, C1-6氰代烷基, C(0) RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, C3-6烯基, C3-6炔 基, 芳基, 杂芳基, 环烷基, 和杂环烷基, 其中所述的 Cw烷基, C 婦基, Cw炔基, 芳基, 杂芳基, 环烷基, 和杂环烷基可选地被 1 , 2, 或 3个独立 选自于卤素, 氨基, ORa, SRa, RbR 基团所取代;或者 R9和 R1Q与同它们连接的原子一起形成一个 5 , 6, 或 7元环的环 烷基或杂环烷基, 并可选地被 1 , 2, 或 3个独立选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯 基, 和 C2_6炔基, 芳基, 杂芳基, 环烷基, 和杂环烷基的基团所取代;R11是氢原子, 卤素, 氨基, ORa, SRa, NRbRc, C1-6烷基, C1-6羟烷 基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基;Y选自于吡啶基, 嘧啶基, 哒嗪基, 吡嗪基, 三嗪基, 噻唑基, 异噻 唑基, 咪唑基, 噁唑基, 异噁峻基, 三唑基, 或吡峻基, 并可选地被 1 , 2, 或 3个 R4所取代;Z选自于吡啶基, 嘧啶基, 哒嗪基, 吡嗪基, 三嗪基, 噻唑基, 异噻唑 基, 咪唑基, 噁唑基, 异噁峻基, 三唑基, 吡峻基, 氮噁峻基, 吡咯并吡啶 基, 吡咯并嘧啶基, 吡唑并吡啶基, 吡唑并嘧啶基, 喹啉基, 异喹啉基, 喹 唑啉基, 哌嗪基, 或吗啉基, 并可选地被 1 , 2, 或 3个 R5所取代;R4和 R5独立地选自于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6 羟烷基, C1-6卤代烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, Rb(CO)Rd, C(0) RbRc, RbS(0)2Rd, S(0)2 RbRc, C(0)Rd, C(0)ORa, S(0)2Rd, 环烷 基, 杂环烷基, 芳基, 和杂芳基;或者两个 R4基团或两个 R5基团各自与同它们连接的原子一起形成一 个 5, 6, 或 7元环的环烷基或杂环烷基, 并可选地被 1, 2, 或 3个独立选自 于卤素, 氨基, ORa, SRa, RbRc, C1-6烷基, C1-6羟烷基, C1-6卤代烷基, d.6氰代烷基, C2.6婦基, 和 C2.6炔基的基团所取代;Ra, Rb, Rc, 和 Rd独立地选自于氢原子, C1-6烷基, C1-6卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, C2-6炔基, 环烷基, 杂环烷基, 芳基, 和杂芳基;或者 1^和1^与同它们连接的氮原子一起形成 4, 5, 6, 或 7元环的杂 环烷基, 并可选地被 1, 2, 或 3个独立选自于卤素, 氨基, Cw烷基, Ci-6 卤代烷基, C1-6羟烷基, C1-6氰代烷基, C2-6烯基, 和 C2-6炔基, 环烷基, 杂 环烷基, 芳基, 和杂芳基的基团所取代;q是一个从 0到 3的整数。6. 根据权利要求 1-5任一项所述的化合物或药学上可接受的盐或其前药, 其中 所述化合物选自于:1-(4-甲基哌嗪- 1-基) -N-(4-甲基 -3- [(4-吡啶 -3-基嘧啶 -2-基)氨基]苯 基) -2,3-二氢化茚 -5-酰胺;4- {5- [({4-甲基 - 3- [(4-吡啶 - 3-基嘧啶 - 2-基)氨基]苯基 }氨基)羰基] - 2,3 -二氢- 1氢-茚- 1-基}哌嗪- 1-羧酸叔丁酯;N- (4-甲基 - 3- [(4-吡啶- 3-基嘧啶- 2-基)氨基]苯基)- 1-哌嗪- 1-基- 2,3- 二氢化茚 -5-酰胺;1-(4-乙基哌嗪- 1-基)- N- (4-甲基 - 3- [(4-吡啶- 3-基嘧啶- 2-基)氨基]苯 基) -2,3-二氢化茚 -5-酰胺;1 - (4-异丙烷基哌嗪- 1 -基) - N- (4-甲基 - 3 - [(4-吡啶- 3 -基嘧啶- 2-基)氨 基]苯基) -2,3-二氢化茚 -5-酰胺;1- [4- (2-羟乙基)哌嗪- 1-基] -N-(4-甲基 -3 -[(4-吡啶 -3-基嘧啶 -2-基)氨 基]苯基) -2,3-二氢化茚 -5-酰胺;1-(4-乙酰基哌嗪 -1-基) -N-(4-甲基 -3 -[(4-吡啶 -3-基嘧啶 -2-基)氨基] 苯基) -2,3-二氢化茚 -5-酰胺;N- [3 - (4 , 5 ' -二嘧啶- 2-基氨基)- 4-甲基苯基]- 1 - (4-甲基哌嗪- 1 -基) - 2,3-二氢化茚 -5-酰胺;1- [(3S)- 3- (二甲氨基)吡咯烷- 1-基] -N- {4-甲基- 3- [(4-吡啶- 3-基嘧啶- 2-基)氨基]苯基 }- 2,3-二氢化茚 -5-酰胺;1- [(3R)- 3- (二甲氨基)吡咯烷- 1-基]- {4-甲基- 3- [(4-吡啶- 3-基嘧啶 - 2-基)氨基]苯基 }- 2,3-二氢化茚 -5-酰胺;(IS)- 1-(4-甲基哌嗪- 1-基)- N- (4-甲基- 3- [(4-吡啶- 3-基嘧啶- 2-基)氨 基]苯基) -2,3-二氢化茚 -5-酰胺;(1R)- 1-(4-甲基哌嗪- 1-基)- N- (4-甲基 - 3- [(4-吡啶 - 3-基嘧啶- 2-基)氨 基]苯基) -2, 3-二氢化茚 -5-酰胺;(1Λ)-Ν- [3- (4, 5' -二嘧啶 -2-基氨基 )-4-甲基苯基]- 1-(4-甲基哌嗪- 1- 基) -2,3-二氢化茚 -5-酰胺;(1R)-N- [3- (4, 5' -二嘧啶 -2-基氨基 )-4-甲基苯基]- 1-(4-甲基哌嗪- 1- 基) -2,3-二氢化茚 -5-酰胺;(IS)- 1-(4-甲基哌嗪- 1-基)- N- (4-甲基- 3- [(4-吡啶- 4-基嘧啶- 2-基)氨 基]苯基) -2, 3-二氢化茚 -5-酰胺; 以及(IS)- 1-(4-甲基哌嗪- 1-基)- N- (4-甲基- 3- [(4-吡啶- 3-基嘧啶- 2-基)氨 基]苯基) -2,3-二氢化茚 -5-酰胺硫酸盐。7. 一种药物组合物, 包括权利要求 1-6任一项所述的化合物或其药学上可接受 的盐或其前药, 和至少一种药学上可接受的载体。8. 一种调节蛋白激酶活性的方法, 其中包括将所述蛋白激酶与权利要求 1-6中 任一项所述的化合物或其药学上可接受的盐或其前药接触。9. 根据权利要求 8所述的方法, 其中所述蛋白激酶选自 Abl, Bcr-Abl, c-Kit, 和 PDGFR。10. 根据权利要求 9所述的方法, 其中所述蛋白激酶是突变的激酶, 选自突变的 Abl激酶, Bcr- Abl激酶, c-Kit激酶和 PDGFR激酶。11. 根据权利要求 1-6任一项所述的化合物或其药学上可接受的盐在制备用于治 疗疾病或失调的药物中的应用, 其中所述疾病或失调是与蛋白激酶活性相关 的或与细胞增殖异常相关的。12. 根据权利要求 11所述的应用,其中所述与蛋白激酶相关的疾病或失调选自癌 症, 炎症, 自身免疫性疾病, 代谢性疾病, 感染, 中枢神经系统疾病和心血 管疾病。13. 根据权利要求 12 所述的应用, 其中所述疾病或失调是与细胞增殖异常相关 的, 为各种癌症。14. 根据权利要求 13所述的应用,其中所述疾病或失调选自白血病,骨髓增生性 疾病, 血液病, 胃肠道间盾瘤, 结肠癌, 乳腺癌, 胃癌, 卵巢癌, 宫颈癌, 肺癌, 肾癌, 前列腺癌, 膀胱癌, 胰腺癌, 神经胶母细胞瘤, 肥大细胞肿瘤, 脑瘤, 生殖细胞肿瘤, 黑色素瘤, 恶瘤, 肉瘤, 包括隆突性皮肤纤维肉瘤。15. 根据权利要求 12所述的应用,其中所述疾病或失调选自自身免疫性疾病和炎 症性疾病。16. 根据权利要求 15所述的应用, 其中所述疾病或失调选自糖尿病, 皮肤炎症, 类风湿关节炎, 过敏性鼻炎, 哮喘, 强直性脊柱炎, 牛皮癣, 和克罗恩病。17. 根据权利要求 12所述的应用,其中所述疾病或失调选自血管疾病和纤维化的 疾病。18. 根据权利要求 17所述的应用,其中所述疾病或失调选自动脉粥样硬化,血管 狭窄, 肺动脉高压, 视网膜疾病, 肺间盾纤维化, 肝硬化, 硬皮病, 肾小球 硬化, 和心月几纤维化。
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CN114573591A (zh) * | 2022-04-16 | 2022-06-03 | 成都施贝康生物医药科技有限公司 | 一种取代的吡咯并嘧啶化合物及其应用 |
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CN102584830A (zh) * | 2011-12-30 | 2012-07-18 | 北京赛林泰医药技术有限公司 | 二氢化茚酰胺化合物、其药物组合物及其用途 |
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CN103373984A (zh) * | 2012-04-24 | 2013-10-30 | 哈尔滨誉衡药业股份有限公司 | 一种二氢化茚酰胺化合物晶型、制备方法及其用途 |
CN102807558A (zh) * | 2012-08-29 | 2012-12-05 | 浙江大德药业集团有限公司 | 作为蛋白激酶抑制剂的含氟二氢化茚酰胺类化合物 |
JP6463366B2 (ja) | 2013-10-10 | 2019-01-30 | イースタン バージニア メディカル スクール | 12−リポキシゲナーゼ阻害物質としての4−((2−ヒドロキシ−3−メトキシベンジル)アミノ)ベンゼンスルホンアミド誘導体 |
ES2670550T3 (es) | 2013-10-14 | 2018-05-30 | Eisai R&D Management Co., Ltd. | Derivados de quinolina selectivamente sustituidos |
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CN104045632B (zh) * | 2014-06-03 | 2016-09-07 | 辽宁大学 | 抗肿瘤药物苯并二氢吡喃(噻喃)酰胺类化合物及其药学上可接受的盐及制备方法和应用 |
MA49014A (fr) | 2017-03-21 | 2020-02-05 | Arbutus Biopharma Corp | Dihydroindène-4-carboxamides substitués, leurs analogues et procédés d'utilisation correspondant |
CN110833547A (zh) * | 2018-08-15 | 2020-02-25 | 广西梧州制药(集团)股份有限公司 | 吡唑并嘧啶衍生物在治疗类风湿关节炎的用途 |
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EP2385035A4 (en) | 2013-07-10 |
NZ593295A (en) | 2012-12-21 |
KR20110099332A (ko) | 2011-09-07 |
AU2009329640B2 (en) | 2015-06-25 |
PL2385035T3 (pl) | 2014-11-28 |
EP2385035A1 (en) | 2011-11-09 |
EP2385035B1 (en) | 2014-06-25 |
US20110319420A1 (en) | 2011-12-29 |
RU2528408C2 (ru) | 2014-09-20 |
UA106057C2 (uk) | 2014-07-25 |
WO2010072166A1 (zh) | 2010-07-01 |
ZA201104523B (en) | 2012-03-28 |
CA2748289A1 (en) | 2010-07-01 |
AU2009329640A1 (en) | 2011-06-30 |
MX2011006724A (es) | 2011-07-13 |
IL213141A (en) | 2014-12-31 |
CN101759683A (zh) | 2010-06-30 |
CA2748289C (en) | 2015-08-18 |
JP2012513956A (ja) | 2012-06-21 |
US8703771B2 (en) | 2014-04-22 |
IL213141A0 (en) | 2011-07-31 |
ES2502941T3 (es) | 2014-10-06 |
CN101925572B (zh) | 2011-12-28 |
JP5707335B2 (ja) | 2015-04-30 |
CN101759683B (zh) | 2011-12-28 |
BRPI0923728A2 (pt) | 2019-09-24 |
HK1163054A1 (zh) | 2012-09-07 |
KR101612115B1 (ko) | 2016-04-12 |
RU2011125376A (ru) | 2013-01-27 |
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