Synthesis and biological activities of novel nonpeptide angiotensin II receptor antagonists based on benzimidazole derivatives bearing a heterocyclic ring

• Published in: Bioorganic & medicinal chemistry Vol. 16; no. 24; pp. 10301 - 10310
• Main Authors: Guo, Xing-Zhou, Shi, Lin, Wang, Rui, Liu, Xiao-Xiao, Li, Bo-Gang, Lu, Xiao-Xia
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.12.2008; Elsevier
• Subjects: Adrenal Cortex - drug effects; Adrenal Cortex - metabolism; Angiotensin Receptor Antagonists; Animals; Antihypertensive agents; Antihypertensive Agents - chemical synthesis; Antihypertensive Agents - chemistry; Antihypertensive Agents - pharmacology; Benzimidazole derivatives bearing a heterocyclic ring; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Biological activity; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Cattle; Dogs; Heart Rate - drug effects; Heterocyclic Compounds, 1-Ring - chemistry; Inhibitory Concentration 50; Medical sciences; Nonpeptide angiotensin II receptor antagonists; Pharmacology. Drug treatments; Receptors, Angiotensin - metabolism; Synthesis; Benzimidazole derivatives bearing a heterocyclic ring; Synthesis; Nonpeptide angiotensin II receptor antagonists; Biological activity; Imidazole derivatives; Systolic pressure; Diastolic pressure; Non peptide compound; Angiotensin II; Chemical synthesis; Dog; Fissipedia; Carnivora; Imidazoline derivatives; AT1 angiotensin receptor; In vitro; Telmisartan; In vivo; Vertebrata; Mammalia; Benzimidazole derivatives; Biphenyl derivatives; Animal; Antihypertensive agent; Angiotensin antagonist
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.10.040

The synthesis and biological activities of a new series of benzimidazole derivatives bearing a heterocyclic ring as AT 1 receptor antagonists is described. 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.