Synthesis and angiotensin converting enzyme-inhibitory activity of N-[(1S)-1-carboxy-5-(4-piperidyl)pentyl]-L-alanine derivatives.
As part of a search for potent and long-lasting angiotensin converting enzyme (ACE) inhibitors, various types of N-[(1S)-1-carboxy-5-(4-piperidyl)pentyl]-L-alanine derivatives (7a, 8-11) were prepared. The key synthetic intermediate, N-[(1S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1- ethoxycarbonylpentyl]-L-alanine (17a), was synthesized by asymmetric reduction of the alpha-oxoester (13) with Lactobacillus paracasei subsp. paracasei followed by a substitution reaction with tert-butyl L-alaninate (15) and subsequent treatment with hydrogen chloride. Compounds 7a and 8-11 showed potent and long-lasting ACE-inhibitory activity in rats.
Kori
M
M
Pharmaceutical Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Itoh
K
K
Inada
Y
Y
Katoh
T
T
Sumino
Y
Y
Nishikawa
K
K
Sugihara
H
H
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D010880:Piperidines; D000409:Alanine