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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-05, Vol.17 (10), p.2921-2926
Main Authors: Xu, Jin Yi, Zeng, Yi, Ran, Qian, Wei, Zhen, Bi, Yi, He, Qian Hui, Wang, Qiu Juan, Hu, Song, Zhang, Jing, Tang, Ming Yue, Hua, Wei Yi, Wu, Xiao Ming
Format: Article
Language:English
Subjects:
Administration, Oral
Angiotensin II Type 1 Receptor Blockers - chemical synthesis
Angiotensin II Type 1 Receptor Blockers - pharmacology
Animals
Antihypertensive agents
Biological and medical sciences
Cardiovascular system
Medical sciences
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
Rats
Rats, Inbred SHR
Structure-Activity Relationship
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2007.02.042