Studies On Design And Synthesis Of Nonpeptide Angiotensin Ⅱ Receptor Antagonists 1, 4-Substituted Indoles Compounds

The renin-angiotensin system（RAS） is recognized as a key element in blood pressure regulation and electrolyte/fluid homeostasis,which is the research starting point of new antihypertensive drugs development.AngⅡreceptor blockade,offers a highly specific approach to inhibition of the system regardless of the source of AngⅡ.Also,since ACE would not be affected by such agents,potentiation of bradykinin and hence cough or angioedema by this mechanism would not be expected during therapy with an AngⅡblocker.ARB can reduce the blood by acting on Angll receptor directly and has long duration of action,which is a very promising antihypertensive drugs.By studying AT₁-Selective Nonpeptidic Antagonists’ space structures,receptor binding state and SAR etc.A series of new compounds were designed by the application of principle of bioisosterism,hybrid approach,reasonable principles of drug design,bioinformatics principle and computer software-assisted drug design etc.This article has designed six different synthetic route and target compounds are new compounds.In this paper,The efficient synthesis of target compounds was obtained starting from 4-methyl-1H-indole.The strategy of the target compounds was cut off from the chemical bond between indole ring and benzene ring,and the key step was accomplished through NBS brominating.After acylation and NBS brominating,linking 2-n-Propyl-4-methyl-6-（1’-methyl-benzimidazole-2-yl）benzimidazole,L-Valine methyl ester and cis-2,6-Dimethyl- morpholine and then gaining the target compounds by Acylation,Deprotection reaction,Coupling reaction, Hydrolysis reaction and Azide reaction.Seven target compounds have designed and synthesized firstly and characterized by ¹HNMR and ESI.