Design, synthesis and optimization of novel Alk5 (activin-like kinase 5) inhibitors

  • Bioorg Med Chem Lett. 2016 Sep 1;26(17):4334-9. doi: 10.1016/j.bmcl.2016.07.030.
Haixia Wang  1 ,  J David Lawson  1 ,  Nick Scorah  1 ,  Ruhi Kamran  1 ,  Mark S Hixon  1 ,  Joy Atienza  1 ,  Douglas R Dougan  1 ,  Mark Sabat  1
Affiliations
  • 1. Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
PMID: 27460209 DOI: 10.1016/j.bmcl.2016.07.030
Abstract

Using SBDD, a series of 4-amino-7-azaindoles were discovered as a novel class of ALK5 inhibitors that are potent in both ALK5 enzymatic and cellular assays. Subsequently a ring cyclization strategy was utilized to improve ADME properties leading to the discovery of a series of 1H-imidazo[4,5-c]pyridin-2(3H)-one drug like ALK5 inhibitors.

Keywords
Activin; Alk5; Factor; Growth; Inhibitors; Kinase; SBDD; Transforming.
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