Design, Synthesis, and Evaluation of Novelly Substituted Benzimidazole Compounds as Angiotensin II Receptor Antagonists.

Abstract

Antagonists. -Compound (VIII) shows the highest angiotensin II receptor antagonistic activity of all tested compounds and is more active than losartan and candesartan (no yields given). -(BALI, A.; BANSAL, Y.; SUGUMARAN, M.; SAGGU, J. S.; BALAKUMAR, P.; KAUR, G.; BANSAL, G.; SHARMA, A.; SINGH, M.; Bioorg. Med. Chem. Lett. 15 (2005) 17, 3962-3965; Dep. Pharm. Sci. Drug. Res., Punjabi Univ., Patiala 147 002, India; Eng.) -C. Oppel 50-122

Synthesis and biological evaluation of some new benzimidazoles derivatives 4'-{5-amino-2-[2-substituted-phenylamino)-phenyl-methyl]-benzimidazol-1 ylmethyl}-biphenyl-2-carboxylic acid: Nonpeptide angiotensin II receptor antagonists.

“…Biological activity of synthesized compounds was carried out using rat blood pressure measurement experiment; the maximum fall blood pressure produced by Losartan is from value 172mm Hg to 113 mm Hg over a period 90 minutes .compounds number, 5, 8,9 also duration 90 minutes. The compounds reported in this paper Compound 1,3,5,6,8,10,12,14,15, and 17were the final compound and prepared for antihypertensive activity.…”

“…No less effort has been devoted to finding AII antagonists, which besides being the most direct way of controlling the RAS could have the additional advantage of lacking the side effects, such as cough and angioedema, observed with ACE inhibitors, as these are probably caused by partial inhibition of the cleavage of bradykinin and substance P. Starting from the initial leads reported by Takeda [9] researchers at DuPont discovered losartan, the first orally active AT1 selective nonpeptide AII antagonist that reached the market for the treatment of hypertension (1994, Cozaar). The substituent at 6-position on the nucleus increases the activity whereas small substituent at 5-position decreases the activity [10]. Compounds containing tetrazole nucleus are also reported as AT 1 receptor antagonists and their protypical derivative exhibits non-competitive antagonism [11] and amino group attach with carboxylic group given good biological activity [11][12].…”

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“…Replacement of the imidazole ring of losartan with heterocyclic ring also led to synthesis of many nonpeptide AT 1 antagonists. In-house 5-nitrobenzimidazole derivatives with varying substituents at 2-position, which have been designed, and synthesized have shown modest affinities for angiotensine II AT1 receptor 8 .…”

Benzimidazoles derivatives with (2-{6-Chloro-5-nitro-1-[2-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] 1H-benzoimidazol-2-yl}-phenyl)-(substituted-benzylidene)-amine with potential angiotensin II receptor antagonists as antihypertensive activity.

“…Thus, reducing the levels of AII by inhibition of one of the RAS enzymes or directly blocking the AII receptors is in theory a good approach for treating hypertension, confirmed by the success of angiotensin-converting enzyme (ACE) inhibitors as antihypertensive [8]. Substantial effort has been made to find renin inhibitors, although orally active agents have only recently been reported [9].The discovery of potent and orally active nonpeptide Ang II antagonists such as losartan and eprosartan has encouraged the development of a large number of similar compounds [10][11][12]. …”