Document Detail

Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 2, optimization for blood pressure reduction in spontaneously hypertensive rats.
MedLine Citation:
PMID:  20678931     Owner:  NLM     Status:  MEDLINE    
Phenylglycine substituted isoquinolones 1 and 2 have previously been described as potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this series to improve metabolic stability and rat oral exposure. Piperidine analog 20 which demonstrates sustained blood pressure normalization in an SHR blood pressure reduction model was identified through this effort.
John D Ginn; Todd Bosanac; Rhonda Chen; Charles Cywin; Eugene Hickey; Mohammed Kashem; Steven Kerr; Stanley Kugler; Xiang Li; Anthony Prokopowicz; Sabine Schlyer; James D Smith; Michael R Turner; Frank Wu; Erick R R Young
Publication Detail:
Type:  Journal Article     Date:  2010-08-01
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  5153-6     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
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MeSH Terms
Blood Pressure / drug effects*
Isoquinolines / chemistry,  pharmacology*
Models, Molecular
Protein Kinase Inhibitors / chemistry,  pharmacology*
Rats, Inbred SHR
Structure-Activity Relationship
rho-Associated Kinases / antagonists & inhibitors*
Reg. No./Substance:
0/Isoquinolines; 0/Protein Kinase Inhibitors; EC Kinases

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