Substituted Benzimidazole Derivatives as Angiotensin II -AT1 Receptor Antagonist: A Review

V.      K. Vyas; M.      Ghate

doi:10.2174/138955710793564151

Abstract

The renin angiotensin system (RAS) plays an important role in regulation of blood pressure and fluidelectrolyte homeostasis. The renin-angiotensin system consists of a cascade of enzymatic reactions producing angiotensin II (Ang II). Ang II is a vasoconstrictive peptide hormone that exerts a wide variety of physiological actions on cardiovascular, renal, endocrine and central nervous systems. The RAS can be inhibited at various points to control pathogenesis of hypertension. Renin inhibitors and angiotensin-converting enzyme (ACE) inhibitors were the earliest RAS blocking agents. A relatively new class of compounds known as Ang II receptor antagonists (SARTANs) is developed for the treatment of hypertension. They exert their action by blocking the binding of Ang II on AT1 receptor. Angiotensin converting enzyme (ACE) inhibitors are associated with incident of side effects such as cough and angioedema while clinical trials with Ang II receptor antagonists have confirmed that these drugs are safe and efficacious for the treatment of hypertension. Based upon the understanding of molecular interaction of Ang II receptor antagonists with AT1 receptor some of the common structural features have been identified, such as a heterocyclic (nitrogen atom) ring system, an alkyl side chain and an acidic tetrazole group. Research efforts for development of new molecules with similar structural features have led to the discovery of various non-peptidic Ang II receptor antagonists with different substituted heterocylic such as imidazole (losartan) and benzimidazole (candesartan and telmisaratn). In this study we have critically reviewed various benzimidazole substituted compounds as Ang II- AT1 receptor antagonists and explored other potential clinical uses for this class of compounds.

Keywords: Angiotensin II, AT1 receptor, AT2 receptor, ACEIs, Ang II receptor blockers, substituted benzimidazole derivatives, Benzimidazole, renin angiotensin system, blood pressure, fluidelectrolyte homeostasis, vasoconstrictive peptide hormone, central nervous systems, RAS, angiotensin-converting enzyme, hypertension, Ang II receptor antagonists, acidic tetrazole group, imidazole, losartan, candesartan, telmisaratn, ACEIs, Ang II receptor blockers, homeostasis, octapeptide Ang II, aldosterone secretion, renal sodium retention, RAS blocking agents, renovascular hypertension, juxtaglomerular, catecholamines, P-Adrenergic receptor, visceral adipose tissue, zinc protease, zona glomerulosa, aldosterone, neurosynaptic transmission, G protein-coupled receptor, tyrosine phosphatases, phospholipase A2, ?? blockers, bradykinin, Renin Inhibitors, Pepstatin, aliskiren, prostaglandins, proteinuria, lisinopril, benazepril, quinapril, ramipril, perindopril, cilazapril,, trandolapril, imidazoles derivatives, telmisartan, valsartan, tasosartan, milfasartan, zolasartan, olmesartan irbesartan, saprisartan, TCV-116, BIBR-277