| Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action. | |
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MedLine Citation:
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PMID: 2194033 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 33 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1990 Jul |
Date Detail:
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Created Date: 1990-08-06 Completed Date: 1990-08-06 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1962-9 Citation Subset: IM |
Affiliation:
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Abbott Laboratories, Cardiovascular Research Division, Abbott Park, Illinois 60064. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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