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Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): optimization for JNK potency and physicochemical properties.

Abstract：

:A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Gong L,Han X,Silva T,Tan YC,Goyal B,Tivitmahaisoon P,Trejo A,Palmer W,Hogg H,Jahagir A,Alam M,Wagner P,Stein K,Filonova L,Loe B,Makra F,Rotstein D,Rapatova L,Dunn J,Zuo F,Dal Porto J,Wong B,Jin S,Chang A,T

doi

10.1016/j.bmcl.2013.04.029

subject

Has Abstract

pub_date

2013-06-15 00:00:00

pages

3565-9

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00510-6

journal_volume

23

pub_type

信件

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