Synthesis and evaluation of novel nonpeptide angiotensin II receptor antagonists: imidazo[4,5-c]pyridine derivatives with an aromatic substituent.
Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4,5-c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4,5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4,5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats.
Kiyama
R
R
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Fuji
M
M
Hara
M
M
Fujimoto
M
M
Kawabata
T
T
Nakamura
M
M
Fujishita
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines