Document Detail


Renin inhibitors containing alpha-heteroatom amino acids as P2 residues.
MedLine Citation:
PMID:  1552498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of renin inhibitors having alpha-heteroatom amino acids as P2 substitutions has been prepared. Examples where the heteroatom is oxygen, sulfur, or nitrogen are described. Many of the compounds exhibit subnanomolar potency when tested in vitro against monkey renin. When selected compounds were tested orally in conscious, salt-depleted, normotensive, Cynomolgus monkeys, low to moderate blood pressure lowering was observed. At an oral dose of 30 mg/kg, compound 53a lowered blood pressure by a maximum of 18 mmHg at 2.5 h post-dose.
Authors:
J T Repine; J S Kaltenbronn; A M Doherty; J M Hamby; R J Himmelsbach; B E Kornberg; M D Taylor; E A Lunney; C Humblet; S T Rapundalo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  35     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1992 Mar 
Date Detail:
Created Date:  1992-04-28     Completed Date:  1992-04-28     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1032-42     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48106-1047.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / chemical synthesis*,  pharmacology
Animals
Blood Pressure / drug effects
Cathepsin D / antagonists & inhibitors
Cattle
Glyoxylates / chemical synthesis*,  pharmacology
Macaca fascicularis
Male
Models, Molecular
Renin / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Glyoxylates; EC 3.4.23.15/Renin; EC 3.4.23.5/Cathepsin D

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


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