发明名称 Therapeutic compounds and compositions
摘要 Compounds of general formula I:; and compositions comprising compounds of general formula I that modulate pyruvate kinase are described herein. Also described herein are methods of using the compounds that modulate pyruvate kinase in the treatment of diseases.
申请公布号 US9108921(B2) 申请公布日期 2015.08.18
申请号 US201414210583 申请日期 2014.03.14
申请人 AGIOS PHARMACEUTICALS, INC 发明人 Cianchetta Giovanni;Popovici-Muller Janeta;Zahler Robert;Cao Sheldon;Wang Xiaolei;Ye Zhixiong
分类号 A61K31/4709;C07D401/12;C07D211/52;C07D401/14;C07D417/12;C07D413/12;C07D211/48;C07D405/12;C07D417/14 主分类号 A61K31/4709
代理机构 Lando & Anastasi LLP 代理人 Lando & Anastasi LLP
主权项 1. A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: A is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted, and the aryl or heteroaryl is optionally fused to an optionally substituted carbocyclyl or an optionally substituted heterocyclyl; X is selected from —NH—S(O)2—, —NH—S(O)2—CH2—, —CH2—S(O)—NH— or —CH2—S(O)2—NH—; Y is C(H) or N; provided that no more than two Y groups are N; R1a is hydroxyl, —CH2OH, —CHO, —CO2H or —CO2—C1-6 alkyl; R1b is C1-8 alkyl optionally substituted with one to four R5 groups; C1-8 alkenyl optionally substituted with one to four R5 groups; cycloalkyl; heterocycle; aryl; heteroaryl; cycloalkylalkyl; cycloalkylalkenyl; heterocyclylalkyl; heterocyclylalkenyl; aralkyl; aralkenyl; heteroaralkyl; heteroaralkenyl; or —OH, with the proviso that when R1a is OH, R1b is not OH; wherein each cycloalkyl, heterocycle, aryl, heteroaryl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclylalkyl, heterocyclylalkenyl, aralkyl, aralkenyl, heteroaralkyl, or heteroaralkenyl is optionally substituted; each R2 is independently selected from halo, alkyl, CN, OH, and alkoxy, wherein said alkyl or alkoxy is optionally substituted with one to four R5 groups; or two adjacent R2 groups are taken together with the ring atoms they are attached to form a 5- or 6-membered carbocyclic, aryl, heterocyclic or heteroaryl ring; each R4 is independently selected from halo, alkyl, alkoxy, haloalkyl, haloalkoxy and hydroxyl; each R5 is independently selected from halo, OH, C1-6 alkoxy, CN, NH2, —SO2—C1-6 alkyl, -NH(C1-6 alkyl), and —N(C1-6 alkyl)2; n is 0, 1, 2 or 3; and m is 0, 1 or 2; provided that a compound of Formula (I) is not the following: (1) 4-[[4-hydroxy-4-(4-methylphenyl)-1-piperidinyl]carbonyl]-N-2-thiazolyl-benzenesulfonamide; (2) 4-[[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]carbonyl]-N-2-thiazolyl-benzenesulfonamide; (3) 4-[[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]carbonyl]-N-2-thiazolyl-benzenesulfonamide; (4) 4-[[4-(2-fluoro-5-methylphenyl)-4-hydroxy-1-piperidinyl]carbonyl]-N-2-thiazolyl-benzenesulfonamide; (5) 4-phenyl-1-[4-[(phenylamino)sulfonyl]benzoyl]-4-piperidinecarboxylic acid methyl ester; (6) 1-[4-[[(2-methylphenyl)amino]sulfonyl]benzoyl]-4-phenyl-4-piperidinecarboxylic acid methyl ester; (7) 1-[4-[methyl[(4-methylphenyl)sulfonyl]amino]benzoyl]-4-phenyl-4-piperidinecarboxylic acid; (8) 1-[4-[(methylphenylamino)sulfonyl]benzoyl]-4-phenyl-4-piperidinecarboxylic acid; (9) 1-[4-[(cyclopropylamino)sulfonyl]benzoyl]-4-phenyl-4-piperidinecarboxylic acid; or (10) 4-phenyl-1-[4-[[(2-thienylmethyl)amino]sulfonyl]benzoyl]-4-piperidinecarboxylic acid methyl ester.
地址 Cambridge MA US