Design, synthesis and biological activity of novel non-peptidyl endothelin converting enzyme inhibitors, 1-phenyl-tetrazole-formazan analogues.
A novel non-peptidyl endothelin converting enzyme inhibitor was obtained through a pharmacophore analysis of known inhibitors and three-dimensional structure database search. Analogues of the new inhibitor were designed using the structure-activity relationship of known inhibitors and synthesized. In anesthetized rats, intraperitoneal administration of the analogues suppressed the pressor responses induced by big endothelin-1.
Yamazaki
Kazuto
K
Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugadenaka, Konohona-ku, 554-0022, Osaka, Japan.
Hasegawa
Hirohiko
H
Umekawa
Kayo
K
Ueki
Yasuyuki
Y
Ohashi
Naohito
N
Kanaoka
Masaharu
M
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005562:Formazans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008666:Metalloendopeptidases; D008958:Models, Molecular; D051381:Rats; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005562:Formazans; D013777:Tetrazoles; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes