Design, synthesis, and evaluation of 5-sulfamoyl benzimidazole derivatives as novel angiotensin II receptor antagonists.
A series of 5-alkylsulfamoyl benzimidazole derivatives have been designed and synthesized as novel angiotensin II (Ang II) receptor antagonists. The compounds have been evaluated for in vitro Ang II antagonism and for in vivo antihypertensive activity on isolated rat aortic ring and desoxycortisone acetate induced hypertensive rats, respectively. The activity is found related to size of alkyl group. The maximum activity is observed with a compact and bulky alkyl group like tert-butyl and cyclohexyl. The compounds 4g and 4h have shown promising both in vitro and in vivo activities. A receptor binding model is also proposed on the basis on the basis of structure-activity relationship in this study.
Kaur
Navneet
N
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Kaur
Amardeep
A
Bansal
Yogita
Y
Shah
Dhvanit I
DI
Bansal
Gulshan
G
Singh
Manjeet
M
D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D015195:Drug Design; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism
D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D044139:Receptor, Angiotensin, Type 2