Synthesis and biological activities of novel nonpeptide angiotensin II receptor antagonists based on benzimidazole derivatives bearing a heterocyclic ring.
A series of benzimidazole derivatives bearing a heterocyclic ring imidazole (1), 5-chloroimidazole (2), 1,2,4-triazol (3), and imidazoline (4) were synthesized and evaluated for angiotensin II antagonistic activities. The synthetic compounds 1-4 were biologically evaluated in vitro using an AT(1) receptor binding assay, where compounds 1 and 3 provided weak binding affinity, compound 2 showed moderate binding affinity, and compound 4 showed good binding affinity. Moreover, compound 4 was found to be almost equipotent with telmisartan in vivo biological evaluation study.
Guo
Xing-Zhou
XZ
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.
Shi
Lin
L
Wang
Rui
R
Liu
Xiao-Xiao
XX
Li
Bo-Gang
BG
Lu
Xiao-Xia
XX
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D020128:Inhibitory Concentration 50; D011945:Receptors, Angiotensin / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D006573:Heterocyclic Compounds, 1-Ring; D011945:Receptors, Angiotensin