Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action
- 1 July 1990
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 33 (7) , 1962-1969
- https://doi.org/10.1021/jm00169a024
Abstract
Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnonamolar 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 severly limited bioavailability.This publication has 4 references indexed in Scilit:
- A new class of orally active glycol renin inhibitors containing phenyllactic acid at P3Biochemical and Biophysical Research Communications, 1989
- Conformationally constrained renin inhibitory peptides: .gamma.-lactam-bridged dipeptide isostere as conformational restrictionJournal of Medicinal Chemistry, 1988
- Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivoJournal of Medicinal Chemistry, 1986
- N-METHYLCEPHALINS .1. SYNTHESIS OF DISTEAROYL L-ALPHA-GLYCERYLPHOSPHORYL-(N-METHYL)ETHANOLAMINE1961