Novel renin inhibitors containing analogs of statine retro-inverted at the C-termini. Specificity at the P2 histidine site
- 1 July 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 30 (7) , 1224-1228
- https://doi.org/10.1021/jm00390a018
Abstract
Substituted 1,3- and 1,4-diamines were prepared from epoxides derived from Boc-leucine or Boc-cyclohexylalanine. These diamines were incorporated into renin inhibitors (IC50 = 4-1500 nM) replacing the Leu-Val scissile bond in small peptide analogues of angiotensinogen. Replacement of the P2 histidine imidazole with other heterocycles maintained or enhanced binding while changing the overall basicity of the inhibitor. Finally, substitution of O-methyltyrosine for the P3 phenylalanine suppressed chymotrypsin cleavage of the P3-P2 bond.This publication has 3 references indexed in Scilit:
- A synthesis of protected aminoalkyl epoxides from .alpha.-amino acidsThe Journal of Organic Chemistry, 1987
- Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analog inhibitors containing a novel analog of statineJournal of Medicinal Chemistry, 1985
- Purification of human renin substrateAnalytical Biochemistry, 1978