Synthesis and angiotensin converting enzyme inhibitory activity of N-carboxymethyldipeptides with an omega-aminoalkyl group.
A series of novel L-alanyl- and L-lysyl-L-proline derivatives having an omega-amino-1-carboxyalkyl group was prepared, and assayed for their inhibitory activity against angiotensin converting enzyme (ACE). The dicarboxylic acids possesing S,S,S configuration showed potent in vitro ACE inhibitory activity with IC50 values of 0.68-1.4 nmol/l. The length of the carbon chain in the omega-aminoalkyl moiety was varied from 6 to 9 to investigate the optimal structure for long-acting ACE inhibitors. The most prolonged activity in vivo was observed with N-[8-amino-1(s)-carboxyoctyl]-L-alanyl-L-proline upon i.v. and p.o.
Saito
S
S
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Matsui
S
S
Watanabe
M
M
Waga
T
T
Kajiwara
Y
Y
Shirota
M
M
Iijima
M
M
Kitabatake
K
K
D000478:Alkylation; D000586:Amination; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008745:Methylation; D015394:Molecular Structure; D011817:Rabbits; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides