Optimization of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists and discussion of their binding modes.
A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V(2) receptor, resulting in the eventual discovery of compound 1g. Molecular modeling of compound 1g with V(2) receptor was also examined to evaluate the binding mode of this series of compounds.
Tsukamoto
Issei
I
Drug Discovery Research, Astellas Pharma Inc, Tsukuba-shi, Ibaraki 305-8585, Japan. issei.tsukamoto@jp.astellas.com
Koshio
Hiroyuki
H
Orita
Masaya
M
Saitoh
Chikashi
C
Yanai-Inamura
Hiroko
H
Kitada-Nozawa
Chika
C
Yamamoto
Eisaku
E
Yatsu
Takeyuki
T
Sakamoto
Shuichi
S
Tsukamoto
Shin-ichi
S
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists*; D013329:Structure-Activity Relationship
D000081:Acetamides; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C030686:acetamide; D001120:Arginine