Document Detail

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:
PMID:  9353891     Owner:  NLM     Status:  MEDLINE    
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.
Y Yamada; K Ando; Y Ikemoto; H Tada; E Shirakawa; E Inagaki; S Shibata; I Nakamura; Y Hayashi; K Ikegami; I Uchida
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Chemical & pharmaceutical bulletin     Volume:  45     ISSN:  0009-2363     ISO Abbreviation:  Chem. Pharm. Bull.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1998-01-02     Completed Date:  1998-01-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0377775     Medline TA:  Chem Pharm Bull (Tokyo)     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  1631-41     Citation Subset:  IM    
Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, Japan.
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MeSH Terms
Administration, Oral
Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*,  pharmacology
Antihypertensive Agents / chemical synthesis*,  pharmacology
Blood Pressure / drug effects*
Cathepsin D / antagonists & inhibitors
Dipeptides / chemistry*
Fatty Alcohols / chemistry*
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
Reg. No./Substance:
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 A; EC; EC D

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

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