发明名称 PYRUVATE KINASE ACTIVATORS FOR USE IN THERAPY
摘要 Described herein are methods for using compounds that activate pyruvate kinase.
申请公布号 US2014155408(A1) 申请公布日期 2014.06.05
申请号 US201214115292 申请日期 2012.05.03
申请人 Su Shin-San Michael 发明人 Su Shin-San Michael
分类号 C12N5/078;C07D451/02;C07D417/12;C07D401/12;C07D405/12;C07D215/36;C07D413/12 主分类号 C12N5/078
代理机构 代理人
主权项 1. A method for increasing lifetime of the red blood cells (RBCs) in need thereof comprising contacting blood with an effective amount of (1) a compound of formula I or a pharmaceutically acceptable salt thereof; (2) a composition comprising a compound of formula I or a salt thereof, and a carrier or (3) a pharmaceutically acceptable composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier: formula (I):  or a pharmaceutically acceptable salt thereof wherein: W, X, Y and Z are each independently selected from CH or N; Q and Q1 are independently selected from a bond or NRb; A is optionally substituted bicyclic aryl or optionally substituted bicyclic heteroaryl; L is a bond, —C(O)—, —(CRcRc)m—, —C(O)—, —(CRcRc)m—OC(O)—, —(CRcRc)m—C(O)—, —NRbC(S)—, or —NRbC(O)— (wherein the point of the attachment to R1 is on the left-hand side); R1 is selected from alkyl, carbocycle, aryl, heteroaryl, and heterocyclyl; each of which is substituted with 0-5 occurrences of Rd; each R3 is independently selected from halo, haloalkyl, alkyl, hydroxyl and —ORa, or two adjacent R3 taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl; each R4 is independently selected from halo, haloalkyl, alkyl, hydroxyl, ═O, —ORa and phenyl, or two R4 taken together with the carbon atoms to which they are attached form a bridged, fused or spyro-fused carbocycle, an aryl or a heteroaryl; each Ra is independently selected from alkyl, acyl, hydroxyalkyl and haloalkyl; each Rb is independently selected from hydrogen and alkyl; each Rc is independently selected from hydrogen, halo, alkyl, alkoxy and halo alkoxy or two Rc taken together with the carbon atoms to which they are attached form an optionally substituted carbocycle; each Rd is independently selected from halo, haloalkyl, haloalkoxy, alkyl, alkynyl, nitro, cyano, hydroxyl, —C(O)Ra, —OC(O)Ra, —C(O)ORa, —SRa, —NRaRb and —ORa, or two Rd taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl; n is 0, 1, or 2; m is 1, 2 or 3; h is 0, 1, 2; g is 0, 1 or 2; the sum of g+h is equal to or greater than 2; and p is 0, 1 or 2.
地址 Newton MA US