| Novel renin inhibitors containing (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol fragment as a transition-state mimic at the P1-P1' cleavage site. | |
MedLine Citation:
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PMID: 9353891 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of renin inhibitors containing the (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol (2-amino-3,5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3,5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10(-8)-10(-10) M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect. |
Authors:
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Y Yamada; K Ando; Y Ikemoto; H Tada; E Shirakawa; E Inagaki; S Shibata; I Nakamura; Y Hayashi; K Ikegami; I Uchida |
Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Chemical & pharmaceutical bulletin Volume: 45 ISSN: 0009-2363 ISO Abbreviation: Chem. Pharm. Bull. Publication Date: 1997 Oct |
Date Detail:
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Created Date: 1998-01-02 Completed Date: 1998-01-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0377775 Medline TA: Chem Pharm Bull (Tokyo) Country: JAPAN |
Other Details:
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Languages: eng Pagination: 1631-41 Citation Subset: IM |
Affiliation:
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Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*, pharmacology Animals Antihypertensive Agents / chemical synthesis*, pharmacology Blood Pressure / drug effects* Callithrix Cathepsin D / antagonists & inhibitors Dipeptides / chemistry* Fatty Alcohols / chemistry* Humans Magnetic Resonance Spectroscopy Pepsin A / antagonists & inhibitors Renin / antagonists & inhibitors*, blood Renin-Angiotensin System / drug effects Sodium Chloride Species Specificity Spectrometry, Mass, Fast Atom Bombardment Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Dipeptides; 0/Fatty Alcohols; 0/N-(1-cyclohexylmethyl-2,4-dihydroxy-5-methylhexyl)-N(alpha)-methyl-N(alpha)-(N-(4-hydroxypiperidino)carbonyl-phenylalanyl)histidinamide; 7647-14-5/Sodium Chloride; EC 3.4.23.1/Pepsin A; 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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