Renin inhibitors. Dipeptide analogs of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond
- 1 October 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 30 (10) , 1729-1737
- https://doi.org/10.1021/jm00393a008
Abstract
A series of dipeptide analogues of angiotensinogen have been prepared and evaluated for their ability to inhibit the aspartic proteinase renin. The compounds were derived from the renin substrate by replacing the scissile amide bond with a transition-state mimic and by incorporating bioisosteric replacements for the Val-10 amide bond. Analogue 21a exhibited an IC50 of 7.6 nM against purified human renin, showed high specificity for this enzyme, and produced a hypotensive response in anesthetized, salt-depleted cynomolgus monkeys.This publication has 8 references indexed in Scilit:
- Novel renin inhibitors containing analogs of statine retro-inverted at the C-termini. Specificity at the P2 histidine siteJournal of Medicinal Chemistry, 1987
- Synthetic and enzyme inhibition studies of pepstatin analogs containing hydroxyethylene and ketomethylene dipeptide isosteresJournal of Medicinal Chemistry, 1987
- Peptide analogues of angiotensinogen effect of peptide chain length on renin inhibitionBiochemical and Biophysical Research Communications, 1986
- Chapter 27. Bioisosterism in Drug DesignPublished by Elsevier ,1986
- Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analog inhibitors containing a novel analog of statineJournal of Medicinal Chemistry, 1985
- Partially modified retro‐inverso peptidesInternational Journal of Peptide and Protein Research, 1983
- Synthesis of analogs of the carboxyl protease inhibitor pepstatin. Effect of structure on inhibition of pepsin and reninJournal of Medicinal Chemistry, 1980
- Purification of human renin substrateAnalytical Biochemistry, 1978