Renin inhibitors containing isosteric replacements of the amide bond connecting the P3 and P2 sites

J S Kaltenbronn; J P Hudspeth; E A Lunney; B M Michniewicz; E D Nicolaides; J T Repine; W H RoarK; M A Stier; F J Tinney; P K Woo

doi:10.1021/jm00164a058

Renin inhibitors containing isosteric replacements of the amide bond connecting the P3 and P2 sites

J Med Chem. 1990 Feb;33(2):838-45. doi: 10.1021/jm00164a058.

Authors

J S Kaltenbronn¹, J P Hudspeth, E A Lunney, B M Michniewicz, E D Nicolaides, J T Repine, W H RoarK, M A Stier, F J Tinney, P K Woo, et al.

Affiliation

¹ Department of Chemistry, Warner-Lambert Company, Ann Arbor, Michigan 48105.

PMID: 2405159
DOI: 10.1021/jm00164a058

Abstract

Renin inhibitors having 13 different isosteres connecting the P3 and P2 positions have been prepared. Synthetic routes and in vitro activity exhibited by these compounds are discussed. The two most potent compounds, 47 and 48, contained the hydroxyethylene isostere, psi [CHOHCH2], and had IC50 values of 61 and 22 nM, respectively.

MeSH terms

Antihypertensive Agents / chemical synthesis
Chemical Phenomena
Chemistry
Chymotrypsin / metabolism
Humans
Hydrolysis
In Vitro Techniques
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / metabolism
Renin / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Antihypertensive Agents
Protease Inhibitors
Chymotrypsin
Renin