Synthesis and biological activity of 2-alkylbenzimidazoles bearing a N-phenylpyrrole moiety as novel angiotensin II AT1 receptor antagonists.
A series of 2-alkylbenzimidazoles bearing a N-phenylpyrrole moiety were synthesized and evaluated as a novel class of AT(1) receptor antagonists. Among them, compounds 10a and 10g inhibited [(125)I] AngII-binding affinity to AT(1) receptor at nanomolar level and potently inhibited the Ang II-induced pressor response by oral administration. Moreover, evaluation in spontaneously hypertensive rats showed that 10a is an orally active AT(1) receptor antagonist.
Xu
Jin Yi
JY
Department of Medicinal Chemistry, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. jinyixu@china.com
Zeng
Yi
Y
Ran
Qian
Q
Wei
Zhen
Z
Bi
Yi
Y
He
Qian Hui
QH
Wang
Qiu Juan
QJ
Hu
Song
S
Zhang
Jing
J
Tang
Ming Yue
MY
Hua
Wei Yi
WY
Wu
Xiao Ming
XM
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D047228:Angiotensin II Type 1 Receptor Blockers