Preparation of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives as novel arginine vasopressin V(2) receptor agonists.
The present work describes the discovery of novel series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin (AVP) V(2) receptor agonists. By replacing the amide juncture in YM-35278 with a direct ring connection gave compound 10a, which acts as a V(2) receptor agonist. These studies provided the potent, orally active non-peptidic V(2) receptor agonists 10a and 10j.
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. issei.tsukamoto@jp.astellas.com
Issei
I
Tsukamoto
Hiroyuki
H
Koshio
Seijiro
S
Akamatsu
Takahiro
T
Kuramochi
Chikashi
C
Saitoh
Takeyuki
T
Yatsu
Hiroko
H
Yanai-Inamura
Chika
C
Kitada
Eisaku
E
Yamamoto
Shuichi
S
Sakamoto
Shin-Ichi
S
Tsukamoto
D000818:Animals; D050034:Antidiuretic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000378:metabolism*; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D008297:Male; D015394:Molecular Structure; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D050034:Antidiuretic Agents; D001552:Benzazepines; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin