Design, Synthesis and In Vivo Cardiovascular Evaluation of Some Novel Aryloxy Propanol Amino Acid Derivatives

Abstract

The design, synthesis and biological evaluation of some aryloxy propanol amino acid derivatives have been described. Synthetic pathways is consisted of the reaction of phenol derivatives with epichlorohydrin and/or epibromohydrin produced the various O‐phenol ether adducts. In continue, the reaction of amino acid with O‐phenol ether adducts generated the new class of β‐blocking agents. The products were evaluated for their cardiovascular property. The 2‐kidney‐1‐clip method was used to induce renovascular hypertension in rats. New analogues of propranolol were evaluated in order to find the most appropriate ones for reducing the hypertension. Our results showed that compound 4 d [i. e.: (2‐hydroxy‐3‐phenoxypropyl) glycine] was effective in blood pressure lowering, even lower than propranolol as a standard drug. All the modelling study was performed at physiological pH (pH∼7.0–7.4).The MEP and docking analysis have shown the appropriate fitting of (2‐hydroxy‐3‐phenoxypropyl) glycine in human β2‐adrenergic receptor active site.