Document Detail


Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action.
MedLine Citation:
PMID:  2194033     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar compound (21) with millimolar solubility. This inhibitor demonstrated excellent efficacy and a long duration of action upon intravenous administration to monkeys. While activity was also observed intraduodenally, a comparison of the blood pressure responses indicated low bioavailability. Subsequent experiments in rats showed that, although the compound was absorbed from the gastrointestinal tract, extensive liver extraction severely limited bioavailability.
Authors:
S H Rosenberg; K W Woods; H L Sham; H D Kleinert; D L Martin; H Stein; J Cohen; D A Egan; B Bopp; I Merits
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  33     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1990 Jul 
Date Detail:
Created Date:  1990-08-06     Completed Date:  1990-08-06     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1962-9     Citation Subset:  IM    
Affiliation:
Abbott Laboratories, Cardiovascular Research Division, Abbott Park, Illinois 60064.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Availability
Blood Pressure / drug effects*
Drug Design
Enzyme Inhibitors / chemical synthesis*,  pharmacokinetics,  pharmacology
Humans
Indicators and Reagents
Macaca fascicularis
Male
Oligopeptides / chemical synthesis*,  pharmacokinetics,  pharmacology
Rats
Rats, Inbred Strains
Renin / antagonists & inhibitors*
Solubility
Structure-Activity Relationship
Tissue Distribution
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Indicators and Reagents; 0/Oligopeptides; EC 3.4.23.15/Renin

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


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