| Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 2, optimization for blood pressure reduction in spontaneously hypertensive rats. | |
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MedLine Citation:
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PMID: 20678931 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article Date: 2010-08-01 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 20 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-16 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 5153-6 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. john.Ginn@boehringer-ingelheim.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects* Isoquinolines / chemistry, pharmacology* Models, Molecular Protein Kinase Inhibitors / chemistry, pharmacology* Rats Rats, Inbred SHR Structure-Activity Relationship rho-Associated Kinases / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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0/Isoquinolines; 0/Protein Kinase Inhibitors; EC 2.7.11.1/rho-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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