Document Detail


Optimization of orally bioavailable alkyl amine renin inhibitors.
MedLine Citation:
PMID:  19959358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension.
Authors:
Zhenrong Xu; Salvacion Cacatian; Jing Yuan; Robert D Simpson; Lanqi Jia; Wei Zhao; Colin M Tice; Patrick T Flaherty; Joan Guo; Alexey Ishchenko; Suresh B Singh; Zhongren Wu; Brian M McKeever; Boyd B Scott; Yuri Bukhtiyarov; Jennifer Berbaum; Jennifer Mason; Reshma Panemangalore; Maria Grazia Cappiello; Ross Bentley; Christopher P Doe; Richard K Harrison; Gerard M McGeehan; Lawrence W Dillard; John J Baldwin; David A Claremon
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Publication Detail:
Type:  Journal Article     Date:  2009-12-01
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-04-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  694-9     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Amines / chemical synthesis,  chemistry*,  pharmacokinetics
Animals
Binding Sites
Blood Pressure / drug effects
Carbamates / chemical synthesis,  chemistry*,  pharmacokinetics
Crystallography, X-Ray
Drug Design
Enzyme Inhibitors / chemical synthesis,  chemistry*,  pharmacokinetics
Haplorhini
Humans
Piperidines / chemical synthesis,  chemistry*,  pharmacokinetics
Rats
Rats, Transgenic
Renin / antagonists & inhibitors*,  blood,  metabolism
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Amines; 0/Carbamates; 0/Enzyme Inhibitors; 0/Piperidines; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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