Document Report Card

ID: ALA1124843

Journal: J Med Chem

Title: Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action.

Authors: Rosenberg SH, Woods KW, Sham HL, Kleinert HD, Martin DL, Stein H, Cohen J, Egan DA, Bopp B, Merits I.

Abstract: Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar 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 severely limited bioavailability.

CiteXplore: 2194033

DOI: 10.1021/jm00169a024