Water-Soluble Renin Inhibitors: Design of a Subnanomolar Inhibitor with a Prolonged Duration of Action

Article abstract of DOI:10.1021/jm00169a024

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 gastrointrestinal tract, extensive liver extraction severely limited bioavailability.