Abstract
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-hydroxvisovaleryl-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-OCH3were 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-α-hydroxyisocaproyl-Leu-Val-Phe-OCH3(Ki= 0.23 mM) and L-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3(Ki= 0.3 mM).
Original language | English (US) |
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Pages (from-to) | 666-669 |
Number of pages | 4 |
Journal | Journal of medicinal chemistry |
Volume | 23 |
Issue number | 6 |
DOIs | |
State | Published - Jan 1 1980 |