The synthesis, transformations and biological activity of thieno[2,3-d]pyrimidine derivatives with the carboxylic groups as the substituents in the pyrimidine ring

Abstract

Aim. To reveal the prospects of the search of novel medicinal substances based on the studies of the derivatives of thieno[2,3-d]pyrimidine with the carboxylic groups as the substituents in the pyrimidine ring using the analysis of the published literature data. Results and discussion. The study has shown a wider range of the pharmacological activity of thieno[2,3-d]pyrimidine-2-carboxylic acid derivatives compared to thieno[2,3-d]pyrimidine-4-carboxylic acids, as well as their availability, despite the fact that the number of preparative methods for the synthesis of these substances is rather limited. The most popular method is cyclization of 2-aminothiophene-3-carboxylic acids with ethyl cyanoformate. On the other hand, thieno[2,3-d]pyrimidine-4-carboxylic acid derivatives are presented in even fewer studies and are poorly studied; many of them are difficult to be synthesized and practically are not found in the pharmacological patent literature. Conclusions. The literature data analysis has revealed the small number of efficient synthetic methods suitable for preparation of thieno[2,3-d]pyrimidines with the carboxylic groups as the substituents in the pyrimidine ring, as well as their low availability for the pharmacological studies. It is also noteworthy that the derivatives of thieno[2,3-d]pyrimidine-4-carboxylic acids are even less studied than the related compounds of thieno[2,3-d]pyrimidine-2-carboxylic acid series, and therefore, more attention should be paid to them as the objects for experimental chemistry and pharmacology. Received: 12.08.2020 Revised: 23.09.2020 Accepted: 08.10.2020

Keywords

• thiophene
• pyrimidine
• carboxylic acid