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Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 3, aryl substituted pyrrolidines |
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| Authors: | Todd Bosanac Eugene R. Hickey John Ginn Mohammed Kashem Steven Kerr Stanley Kugler Xiang Li Alan Olague Sabine Schlyer Erick R.R. Young |
| Affiliation: | 1. Department of Medicinal Chemistry, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, United States;2. Department of Cardiometabolic Diseases, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, United States |
| Abstract: | The discovery and SAR of a series of β-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 β-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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