Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3,4-dihdyro-2(1H)-quinolinone.
A series of compounds has been synthesized and demonstrated to be antagonists of V1 receptors both in vitro and in vivo. These compounds are structurally related to the 1-(4-piperidyl)-2(1H)-quinolinones, including OPC-21268, an orally bioavailable AVP V1 antagonist with high V1 specificity. It has been found that the introduction of an acetamide group on the terminal alkoxy chain of 41-44 leads to an increase in oral activity. Certain of these compounds may have efficacy in the study of AVP V1 receptors.
Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Tokushima, Japan.
H
H
Ogawa
Y
Y
Yamamura
H
H
Miyamoto
K
K
Kondo
H
H
Yamashita
K
K
Nakaya
T
T
Chihara
T
T
Mori
M
M
Tominaga
Y
Y
Yabuuchi
D000284:Administration, Oral; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001665:Binding Sites; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; C068644:OPC 21268