Angiotensin converting enzyme inhibitors. (Mercaptoaroyl)amino acids.
A series of (mercaptoaroyl)amino acids and related compounds was synthesized and tested for ability to inhibit angiotensin converting enzyme (ACE). The most active compound was N-(3-chloro-2-mercaptobenzoyl)-N-cyclopentylglycine, having an in vitro I50 = 0.28 microM. Substitution of the aromatic 3-position by small polar groups enhanced ACE inhibitory activity, whereas bulky groups diminished it. Alteration of the beta relationship between the mercaptan and amide carbonyl or masking of the thiol by acylation reduced activity. Replacement of the thiol by nitro, hydroxy, or carboxy gave compounds lacking ACE inhibitory activity.
Menard
P R
PR
Suh
J T
JT
Jones
H
H
Loev
B
B
Neiss
E S
ES
Wilde
J
J
Schwab
A
A
Mann
W S
WS
D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000494:pharmacology
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D013440:Sulfides