Drapak I. Purposeful search for biologically active substances based on five-membered heterocycles and related heterocyclic systems for the treatment of cardiovascular disease

The dissertation is a comprehensive fundamental research, dedicated to purposeful research on the virtual screening and rational design, synthesis, study of physicochemical properties and pharmacological activity of biologically active substances based on five-membered heterocycles and related heterocyclic systems for the treatment of cardiovascular diseases. On the basis of preliminary calculations and according to the stages of the study design, the pharmacological activity of the synthesized compounds was screened. Screening studies included an analysis of the effects of drug-specific drugs for the treatment of cardiovascular diseases: the active compounds were identified and the basic patterns of structure- activity (cardioprotective, antihypertensive, antioxidant, and diuretic) that were used for purposeful search for compounds were identified. On the basis of calculated molecular descriptors and values of pharmacological activity, the analysis of the quantitative dependence of structure - activity was performed. The resulting QSAR models were used to predict the corresponding activity of the molecules. Conducted pharmacophore modeling allowed to obtain pharmacophore models of cardioprotective, diuretic, antihypertensive activity. The obtained pharmacophore models are used for in silico screening and purposeful search for potential cardioprotectors, diuretics, and antihypertensive agents. Pharmacophore modeling has made it possible to select structures of promising molecules for synthetic studies. Research on the scaling of the synthesis methods of Cardiazole and Urocarb has been carried out; the optimal technological parameters have been established. The block diagram of industrial synthesis has been developed.