N-(α-Hydroxyalkanoyl) Derivatives of Leu-Val-Phe-OCH3 as Inhibitors of Renin

Article abstract of DOI:10.1021/jm00180a017

The following N-(α-hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-α-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-α-hydroxyphenylacetyl-Leu-Val-Phe-OCH3.Analysis of the compounds through the use of Dixon plots showed all of the compounds to be competitive inhibitors of renin.All but D-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were found to be more active than the known tetrapeptideinhibitor Leu-Leu-Val-Phe-OCH3 (1).The two most active compounds of the series were L-α-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (K_i = 0.23 mM) and L-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (K_i = 0.3 mM).