N-(alpha-Hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 as inhibitors of renin.
The following N-(alpha-hydroxylakanoyl) derivatives of Leu-Val-Phe-OCH3 were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-alpha-hydroxyphenylacetyl-Leu-Val-Phe-OCH3. Analysis of the compounds through the use of Dixion plots showed all of the compounds to be competitive inhibitors of renin. All but D-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were found to be more active than the known tetrapeptide inhibitor Leu-Leu-Val-Phe-OCH3 (1). The two most active compounds of the series were L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (Ki = 0.23 mM) and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (Ki = 0.3 mM).
D000650:Amnion / Q000201:enzymology; D000803:Angiotensin I / Q000032:analysis; D006801:Humans; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000803:Angiotensin I; D009842:Oligopeptides; D000092502:Renin Inhibitors