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.
Ogawa
H
H
Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Tokushima, Japan.
Yamamura
Y
Y
Miyamoto
H
H
Kondo
K
K
Yamashita
H
H
Nakaya
K
K
Chihara
T
T
Mori
T
T
Tominaga
M
M
Yabuuchi
Y
Y
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