发明名称 Mixed lineage kinase inhibitors and method of treatments
摘要 Provided herein are imidazopyridine compounds having an inhibitory effect on mixed lineage kinases (MLKs), methods of their synthesis, and methods of their therapeutic. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and pharmaceutical compositions.
申请公布号 US9370515(B2) 申请公布日期 2016.06.21
申请号 US201414201673 申请日期 2014.03.07
申请人 CALIFIA BIO, INC.;UNIVERSITY OF ROCHESTER 发明人 Goodfellow Val S.;Nguyen Thong X.;Ravula Satheesh B.;Gelbard Harris A.
分类号 A61K31/5025;A61K45/06;C07D487/04;C07D513/04;A61K31/427;A61K31/4402;A61K31/513;A61K31/536 主分类号 A61K31/5025
代理机构 Pillsbury Winthrop Shaw Pittman LLP 代理人 Pillsbury Winthrop Shaw Pittman LLP
主权项 1. A compound having the structure of Formula I or a pharmaceutically acceptable isomer, isotope, enantiomer, or salt thereof, wherein J has a structure of  substituted with up to R10, or J has a structure of  optionally substituted with up to four R10, each R10 is independently selected from the group consisting of halo, alkyl, haloalkyl, alkoxy, haloalkoxy, —OH, and —OCOR6; X is NR12 or S; one of X1, X2, X3, and X4 is N and the other three of X1, X2, X3, and X4 are CH; Y is —W—(CH2)n—R1, W is null, phenylene, or —NR6-phenylene, where the NR6 is attached to the imidazopyridazine core structure of Formula I; R1 is —NR2R3, or piperazinyl, where the nitrogen atom of the piperazinyl is optionally substituted with alkyl or alkoxy; R2 is H or alkyl; R3 is selected from the group consisting of C2-C10 alkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, where any atom of R3 is optionally substituted with one or more R7; or R2 and R3 taken together with the N atom to which they are attached form a 3- to 7-membered heterocyclic ring optionally substituted with R8; R4 is H or alkyl; R5 is H, alkyl, or NHR9; R6 is H or alkyl; each R7 is independently alkyl, cycloalkyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, perhaloalkoxy, halo, oxo, —OH, hydroxyalkyl, —COOR11, or —O—(CH2)m—OH; R8 is alkoxy, hydroxyalkyl, or COOR11; R9 is H, alkyl, or cycloalkyl; R11 is H, or alkyl; R12 is H, or alkyl; n is 0 or 1; m is 1, 2, or 3; and p is 1, 2, or 3; with the proviso that if J is an unsubstituted benzothiophene, then R3 is either aryl or heteroaryl, where any atom of R3 is optionally substituted with one or more R7.
地址 San Diego CA US