2. Academic Validation
  3. Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines

Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines

  • Bioorg Med Chem Lett. 2010 Jun 15;20(12):3746-9. doi: 10.1016/j.bmcl.2010.04.069.
Todd Bosanac 1,  Eugene R Hickey,  John Ginn,  Mohammed Kashem,  Steven Kerr,  Stanley Kugler,  Xiang Li,  Alan Olague,  Sabine Schlyer,  Erick R R Young
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877-0368, USA. todd.bosanac@boehringer-ingelheim.com
PMID: 20471253 DOI: 10.1016/j.bmcl.2010.04.069
Abstract

The discovery and SAR of a series of beta-aryl substituted pyrrolidine 2H-isoquinolin-1-one inhibitors of Rho-kinase (ROCK) derived from 2 is herein described. SAR studies have shown that aryl groups in the beta-position are optimal for potency. Our efforts focused on improving the ROCK potency of this isoquinolone class of inhibitors which led to the identification of pyrrolidine 32 which demonstrated a 10-fold improvement in aortic ring (AR) potency over 2.

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