2,3,5-Trisubstituted pyridines as selective AKT inhibitors-Part I: Substitution at 2-position of the core pyridine for ROCK1 selectivity.

Autor: Lin H; Oncology Medicinal Chemistry, GlaxoSmithKline, 1250 S. Collegeville, Rd., Collegeville, PA 19426, United States. hong.2.lin@gsk.com, Yamashita DS, Zeng J, Xie R, Wang W, Nidarmarthy S, Luengo JI, Rhodes N, Knick VB, Choudhry AE, Lai Z, Minthorn EA, Strum SL, Wood ER, Elkins PA, Concha NO, Heerding DA
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Jan 15; Vol. 20 (2), pp. 673-8. Date of Electronic Publication: 2009 Nov 20.
DOI: 10.1016/j.bmcl.2009.11.064
Abstrakt: 2,3,5-Trisubstituted pyridines have been designed as potent AKT inhibitors that are selective against ROCK1 based on the comparison between AKT and ROCK1 structures. Substitution at the 2-position of the core pyridine is the key element to provide selectivity against ROCK1. An X-ray co-crystal structure of 9p in PKA supports the proposed rationale of ROCK1 selectivity.
(Copyright 2009 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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