INVESTIGATION OF THE RELATIONSHIP BETWEEN THE FUNCTIONAL GROUPS OF 2,4-DIOXO- AND 4-IMINO-2-OXO-3-PHENYL-5-R-6-R-THIENO[2,3-d] PYRIMIDINES AND THEIR BIOLOGICAL ACTIVITY

Abstract

The popularity of diuretic agents in modern medicine and their disadvantages lead to the search for new compounds with this activity. Despite the emergence of new diuretic drugs in the healthcare system, significant problems associated primarily with electrolyte disorders remain unresolved. The diuretic effect of 2-alk(acyl)oxy-4-oxo-3-phenyl-5-R-6- R’-thieno[2,3-d]-pyrimidines (in particular, 2-ethoxy-4-oxo-3-phenyl-5,6-trimethylenothieno[2,3-d]pyrimidine and p-2-acetoxy-4-oxo-3-phenyl-5,6-dimethylthieno[2,3-d]pyrimidine) and determined, at the same time, thechemical structure-biological action relationship has not been establishedfor the derivatives of 2,4-dioxo- and 4-imino-2-oxo-3- phenyl-5-R-6-R-thieno[2,3-d]pyrimidines. The aim of this work is to establish the relationship between the functional groups of 2,4-dioxo- and 4-imino-2-oxo-3-phenyl-5-R-6-R-thieno[2,3-d]pyrimidines and their biological activity. Methodology. The diuretic and anti-inflammatory activity was determined in vivo by studying, respectively, the effect of compounds on renal secretory function (reference drug hypothiazide) and on edema reduction in the model of karegenin edema (reference drug voltvren). The antimicrobial effect was studied in vitro on museum strains of microorganisms. Scientific novelty. The relationship between the functional groups of 2,4-dioxo- and 4-imino-2-oxo-3-phenyl-5-R-6- R-thieno[2,3-d]pyrimidines and their biological, in particular diuretic, activity was investigated for the first time. The regularity of ‘functional group – biological action’ for 2,4-dioxo- and 4-imino-2-oxo-3-phenyl-5-R-6-R-thien o[2,3-d] py rimidinederivativesin terms of diuretic, anti-inflammatory and antimicrobialactivity was established. An increase in the diuretic activity of oxo- and imino-derivatives in the presence of a tetramethylene group in the molecule was proved. At the same time, the presence of a dimethylene radical in the oxo-derivatives molecule slightly correlates with the antimicrobial effect of the compounds. The prospect of further study of this series of compounds as potential API diuretics may be related to the studies of compound V – 4-imino-2-oxo-3-phenyl-5,6-trimethylenothieno[2,3-d]pyrimidine.