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发明公开
CN102639496A 赖氨酸特异性脱甲基酶-1抑制剂及其应用 失效 - 权利终止

赖氨酸特异性脱甲基酶-1抑制剂及其应用
摘要：
本发明涉及化学式(I)的化合物：(A’)x-(A)-(B)-(Z)-(L)-(D)，其中：(A)是杂芳基或芳基；每个(A’)，如果存在的话，独立地选自芳基、芳烷氧基、芳烷基、杂环基、芳氧基、卤基、烷氧基、卤代烷基、环烷基、卤代烷氧基、和氰基，其中每个(A’)被0、1、2、或3个取代基取代，所述取代基独立地选自卤基、卤代烷基、芳基、芳烷氧基、烷基、烷氧基、氰基、磺酰基、酰氨基、和亚硫酰基；X是0、1、2、或3；(B)是环丙基环，其中(A)和(Z)共价键合于(B)的不同碳原子；(Z)是-NH-；(L)选自-CH2CH2-、-CH2CH2CH2-、和-CH2CH2CH2CH2-；和(D)选自-N(-R 1)-R2、-O-R3、和-S-R3，其中：R1和R2连同R1和R2所连接的氮原子一起相互连结以形成杂环，其中所述杂环具有0、1、2、或3个取代基，该取代基独立地选自-NH2、-NH(C1-C6烷基)、-N(C1-C6烷基)(C1-C6烷基)、烷基、卤基、氰基、烷氧基、卤代烷基、和卤代烷氧基，或R1和R2独立地选自-H、烷基、环烷基、卤代烷基、和杂环基，其中一起在R1和R2上的取代基的总数为0、1、2、或3个，并且该取代基独立地选自-NH2、-NH(C1-C6烷基)、-N(C1-C6烷基)(C1-C6烷基)、和氟基；以及R3选自-H、烷基、环烷基、卤代烷基、和杂环基，其中R3具有0、1、2、或3个取代基，该取代基独立地选自-NH2、-NH(C1-C6烷基)、-N(C1-C6烷基)(C1-C6烷基)、和氟基；或其对映体、非对映体、或混合物，或其药用盐或溶剂化物。本发明的化合物显示抑制性LSD1活性，其使得它们可用于治疗或预防疾病如癌症。
摘要（英）：

The invention relates to a compound of Formula (I): (A')x-(A)-(B)-(Z)-(L)-(D), wherein: (A) is heteroaryl or aryl; each (A'), if present, is independently chosen from aryl, arylalkoxy, arylalkyl, heterocyclyl, aryloxy, halo, alkoxy, haloalkyl, cycloalkyl, haloalkoxy, and cyano, wherein each (A') is substituted with 0, 1, 2, or 3 substituents independently chosen from halo, haloalkyl, aryl, arylalkoxy, alkyl, alkoxy, cyano, sulfonyl, amido, and sulfinyl; X is 0, 1, 2, or 3; (B) is a cyclopropyl ring, wherein (A) and (Z) are covalently bonded to different carbon atoms of (B); (Z) is -NH-; (L) is chosen from -CH2CH2-, -CH2CH2CH2-, and -CH2CH2CH2CH2-; and (D) is chosen from -N(-R1)-R2, -O-R3, and -S-R3, wherein: R1 and R2 are mutually linked to form a heterocyclic ring together with the nitrogen atom that R1 and R2 are attached to, wherein said heterocyclic ring has 0, 1, 2, or 3 substituents independently chosen from -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C1-C6 alkyl), alkyl, halo, cyano, alkoxy, haloalkyl, and haloalkoxy, or R1 and R2 are independently chosen from -H, alkyl, cycloalkyl, haloalkyl, and heterocyclyl, wherein the sum of substituents on R1 and R2 together is 0, 1, 2, or 3, and the substituents are independently chosen from -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C1-C6 alkyl), and fluoro; and R3 is chosen from -H, alkyl, cycloalkyl, haloalkyl, and heterocyclyl, wherein R3 has 0, 1, 2, or 3 substituents independently chosen from -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C1-C6 alkyl), and fluoro; or an enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or solvate thereof. The compounds of the invention show inhibitory LSD1 activity, which makes them useful in the treatment or prevention of diseases such as cancer.

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