Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site

S H Rosenberg; J F Dellaria; D J Kempf; C W Hutchins; K W Woods; R G Maki; E de Lara; K P Spina; H H Stein; J Cohen

doi:10.1021/jm00168a009

Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site

J Med Chem. 1990 Jun;33(6):1582-90. doi: 10.1021/jm00168a009.

Authors

S H Rosenberg¹, J F Dellaria, D J Kempf, C W Hutchins, K W Woods, R G Maki, E de Lara, K P Spina, H H Stein, J Cohen, et al.

Affiliation

¹ Abbott Laboratories, Cardiovascular Research Division, Abbott Park, Illinois 60064.

PMID: 2187994
DOI: 10.1021/jm00168a009

Abstract

A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol-based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly.

MeSH terms

Carbamates / chemical synthesis
Carbamates / pharmacology*
Chemical Phenomena
Chemistry
Furans / chemical synthesis
Furans / pharmacology*
Heterocyclic Compounds* / chemical synthesis
Heterocyclic Compounds* / pharmacology
Hydrogen Bonding
Lactones / chemical synthesis
Lactones / pharmacology*
Molecular Conformation
Renin / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Carbamates
Furans
Heterocyclic Compounds
Lactones
tetrahydrofuran
Renin