The synthesis and physicochemical properties of new derivatives of 5-r-phenylamino-2-mercapto-1,3,4-thiadiazole

Abstract

In the current realities the healthcare requires development and introduction of original medicines into production along with manufacture of generic drugs -only this way can raise the pharmaceutical industry of Ukraine to the higher level of quality and to rank it together with the leading European states. In this regard, creation of new effective medicines is a rather topical issue of modern pharmacy. Recently, along with the high pharmacological activity, the simplicity of synthetic methods and availability of the chemical raw material, which provide a relatively law prime cost of finished products, become the most important parameters for the choice of the research objects. With the aim of searching for new biologically active substances we paid attention to the derivatives of 1,3,4-thiadizole, which had already shown themselves as high-efficient bioactive substances exhibiting various types of the pharmacological action [2,3,5,6, 8, 10, 11]. Currently, data on promising applications of derivatives of 1,3,4-thiadiazole for treating cancer appear in scientific literature more often [5,[10][11]. At the moment, the fundamental research of new derivatives are conducted on the basis of this heterocycle as potential antimicrobial agents [3, 6] and аnticonvulsants [2, 8]. Thus, the further search of new bioactive substances among the derivatives of 1,3,4-thiadizole is one of the promising directions.The aim of this work was to extend the range of potential bioactive substances on the basis of 5-R-phenylamino-2-mercapto-1,3,4-thiadiazoles. The synthesis of derivatives of 5-R-phenylamino-2-mercapto-1,3,4-thiadiazoles 1.1-1.2 was carried out by the interaction of carbonic disulphide and R-phenylthiosemicarbazide in the dimethylformamide medium at the temperature of 75°C with satisfactory yields (78-80%) by the known method [8].The structure of the compounds obtained was confirmed by modern physical and chemical methods. Formation of the thiadiazole cycle was proven by the absence of NH-NH signal in the 1 Н NMR-spectra of the compounds synthesized at δ 10.60-10.64 ppm and the presence of a singlet of the mercapto group at approximately 3.40 ppm [1, 9].The target compounds -аnilides of 5-(2,5-dimethoxy) phenylamino-1,3,4-thiadiazole-2-yl-thioacetate acid 3.1-3.8 and аmides of 5-phenylamino-1,3,4-thiadiazole-2-ylthioacetate acid 4.1-4.3 were obtained by S-alkylation with anilidies 2.1-2.8 and alkylamides 2.9-2.11 of chloracetate acid.5-R-phenylamino-2-mercapto-1,3,4-thiadiazoles 1.1-1.2 were obtained in ethanol in the presence of the equimolar quantity of potassium hydroxide according to the Scheme given below.The research results have proven that application of the method allows obtaining the target products with satisfactory yields and sufficient purity (Tab. 1). All compounds obtained after crystallization from ethanol are white crystalline substances with distinct melting points, soluble in most organic solvents (Tab. 1). To study the course of the alkylation reaction when using various alkali reagents the amides of ...