The Pharmacophore Studies Of The Sartan Antihypertensive Drugs And The New Compounds Design And Evaluation

The3D-QSAR pharmacophore model of the AT1receptor antagonists was build by learning structure-activity relationship study AT1receptor antagonists. The pharmacophore Hypol was composed by one hydrogen bond receptor, two hydrophobic features, one negative ionizable and one ring aromatic in accordance with a certain three-dimensional space. The model was validated reasonable and good activity prediction capability by data analysis, test set and Fischer’s random verification. The test set’s correlation coefficient is0.880. The database searching proved that the model has strong search capabilities. Hyepolcan be used for searching new compounds and evaluating new compounds. The accuracy of Hypol was further validated by compare with the common structure-based pharmacophore model.The activity of47potential compounds was predicted by the model Hypo1. In addition, a number of compounds was designed based on the principle of bioisostere. The compounds were put into the Discovery Studio2.5to get ADMET analysis using the Hypol, the activity of these compound was predicted. As a result,17compounds were gotten to be synthesized.The synthetic routes of17potential compounds was designed by studying the structural characteristics of them and some synthesis of literatures that refer to similar compounds looking forward to synthesis of these compounds and measure in vitro biological activity.