Research On Structure-activity Relationships And Virtual Combinatorial Chemical Library Design

Antihypertensive non-peptide angiotensin II receptor antagonists have been paid much attention since it was found in 1980's. AII receptor antagonists taking effects by combined with AII receptor and block the biological effect of AII receptor. Compared with other antihypertensive in Renin-angiotensin System, AII receptor antagonists is the most directed drug with better effects and lower vice-effects, which is especial suitable for old man without firstly low blood pressure. The expert forecasted that AII receptor antagonists would become the firstly clinical antihypertensive drugs in the future. Up to now, six AII receptor antagonists have been on markets, and other more than fifty have been on clinical experiments. With the more and more hypertension occurred today, more and more antihypertensive with better effect, shorter effect time, longer lasting time and suitable for all aged man are needed. Therefore the research objective was to analysis the relationship between AII receptor antagonists structure and pharmacodynamics, build chemical combinatorial library with large compounds, then to put forward some improvement opinion about changing structure, and offer some references and help for designing new AII receptor antagonists compounds.Seventy imidazolenes and 113 biphenyltetrazole compounds were selected from literature and their minimum inhibition concentrations to angiotensin II AII receptor had been selected as biological value. The structural parameters of these compounds had been calculated by quantum chemistry AM1 algorithm. The correlative relationship between the structural parameters was analyzed and five structure parameters with higher correlative relationship with biological value were...