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Tetrasubstituted pyridines as potent and selective AKT inhibitors: Reduced CYP450 and hERG inhibition of aminopyridines.

Abstract：

:The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously described trisubstituted pyridines. It also displayed dose-dependent inhibition of both phosphorylation of GSK3beta and tumor growth in a BT474 tumor xenograft model in mice.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Lin H,Yamashita DS,Xie R,Zeng J,Wang W,Leber J,Safonov IG,Verma S,Li M,Lafrance L,Venslavsky J,Takata D,Luengo JI,Kahana JA,Zhang S,Robell KA,Levy D,Kumar R,Choudhry AE,Schaber M,Lai Z,Brown BS,Donovan BT,Mi

doi

10.1016/j.bmcl.2009.11.061

subject

Has Abstract

pub_date

2010-01-15 00:00:00

pages

684-8

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)01631-X

journal_volume

20

pub_type

杂志文章

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