Synthesis and angiotension converting enzyme inhibitory activity of L-lysyl-N-substituted glycine derivatives.
The synthesis and biological activity of novel L-lysyl-N-substituted glycine derivatives which exhibit in vitro and in vivo angiotensin converting enzyme (ACE) inhibition, are described. Particularly, N-[N alpha-(1-carboxy-3-phenylpropyl)-L-lysyl]-N-(4-phenylcyclohexyl)glycine (11e), N-[N alpha-(1-carboxy-3-cyclopentylpropyl)-N epsilon-carbobenzoxy-L- lysyl]-N-cyclopentyl glycine (9h) and N-[N alpha-[1(S)-carboxy-3-cyclohexylpropyl]-L-lysyl]-N-cyclopentyl glycine (19a) showed a strong inhibitory activity at IC50 as low as 0.65, 0.64 and 0.11 nmol/l, respectively. The most potent activity in vivo was observed with the compound 19a after i.v. administration in the rat.
Saito
S
S
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Matsui
S
S
Fukushima
S
S
Watanabe
M
M
Waga
T
T
Kajiwara
Y
Y
Shirota
M
M
Iijima
M
M
Kitabatake
K
K
D000803:Angiotensin I / Q000097:blood / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005998:Glycine; D066298:In Vitro Techniques; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology; D007192:Indenes / Q000138:chemical synthesis*; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008239:Lysine; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; D007192:Indenes; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D008239:Lysine; D005998:Glycine; C047759:delapril