发明名称 7-DEAZAPURINE MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
摘要 Disclosed are compounds, pharmaceutical compositions containing the compounds, uses of the compounds and compositions as modulators of histone methyltransferases, and methods for treating diseases influenced by modulation of histone methyltransferase activity.
申请公布号 US2016251390(A1) 申请公布日期 2016.09.01
申请号 US201514867356 申请日期 2015.09.28
申请人 Epizyme, Inc. 发明人 Chesworth Richard;Kuntz Kevin Wayne;Olhava Edward James;Patane Michael A.
分类号 C07H19/14 主分类号 C07H19/14
代理机构 代理人
主权项 1. A compound of formula I: or a pharmaceutically acceptable salt, hydrate, enantiomer or stereoisomer thereof, wherein independently for each occurrence, X is R1 is hydrogen, alkyl, cycloalkyl, alkylcycloalkyl, alkylaryl, haloalkyl, formyl, heterocyclyl, heterocyclylalkyl,  or (C2-C4)alkyl substituted with  except that when X is  R1 is not R10 is hydrogen or alkyl; R11a is hydrogen, alkyl, or alkyl-cycloalkyl; R11b is hydrogen or alkyl; or taken together with R11a and the nitrogen to which it is attached forms a 4- to 8-membered heterocyclyl comprising 0 or 1 additional heteroatoms; R13 is hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl or silyl; R14 is hydrogen, alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl; R15 is alkyl, cycloalkyl or cycloalkylalkyl; R20 is hydrogen, alkyl, cycloalkyl or cycloalkylalkyl; A is R2 is Y is —NH—, —N(alkyl)-, —O—, or —CR62—; R22a is aryl, heteroaryl, aralkyl, heteroaralkyl, fused bicyclyl, biaryl, aryloxyaryl, heteroaryloxyaryl, aryloxyheteroaryl or heteroaryloxyheteroaryl; R22b is hydrogen or alkyl; R24 is hydrogen or alkyl; R25a, R25b, R25c, and R25d independently are -M2-T2, in which M2 is a bond, SO2, SO, S, CO, CO2, O, O—C1-C4 alkyl linker, C1-C4 alkyl linker, NH, or N(Rt), Rt being C1-C6 alkyl, and T2 is H, halo, or RS4, RS4 being C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 8-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, and each of 0-C1-C4 alkyl linker, C1-C4 alkyl linker, Rt, and RS4 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl; R3 is hydrogen, halogen, hydroxy, alkyloxy, aralkyloxy, alkylcarbonyloxy or silyloxy; R4 is hydrogen, halogen, hydroxy, alkyloxy, aralkyloxy, alkylcarbonyloxy or silyloxy; R41 is hydrogen, alkyl or alkynyl; Z is hydrogen or R5a is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, biaryl, alkenylalkyl, alkynylalkyl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, heteroaralkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, aralkylcarbonylaminoalkyl, aryl sulfonylaminoalkyl, alkylthioalkyl, aralkylthioalkyl or heteroaralkylthioalkyl; or alkyl substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, halo, carboxy, alkyoxy, aryloxy, aralkyloxy, nitro, amino, amido, aryl and heteroaryl; R5b is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, biaryl, alkenylalkyl, alkynylalkyl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, heteroaralkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, aralkylcarbonylaminoalkyl, aryl sulfonylaminoalkyl, alkylthioalkyl, aralkylthioalkyl or heteroaralkylthioalkyl; or alkyl substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, halo, carboxy, alkyoxy, aryloxy, aralkyloxy, nitro, amino, amido, aryl and heteroaryl; or taken together with R5a and the nitrogen to which it is attached forms a 4- to 8-membered heterocyclyl comprising 0 or 1 additional heteroatoms; R6 is hydrogen, alkyl or halo; or two geminal R6 taken together are ethylene, propylene or butylene; R7a is hydrogen, lower alkyl, lower haloalkyl, cyano, halo, lower alkoxy, or C3-C5 cycloalkyl, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cyano, lower alkoxy and halo; R7b is hydrogen, lower alkyl, lower haloalkyl, cyano, halo, lower alkoxy, or C3-C5 cycloalkyl, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cyano, lower alkoxy and halo; and R7c is hydrogen, lower alkyl, lower haloalkyl, cyano, halo, lower alkoxy, or C3-C5 cycloalkyl, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cyano, lower alkoxy and halo.
地址 Cambridge MA US