Synthesis and antimicrobial screening of novel 2-thiopyrimidine derivatives bearing a pyrazole moiety

2-Thiouracil-5-carbonitrile derivatives 2a,b were used as starting material for synthesis of the chloropyrimidines 3a,b , and then reacted with thiourea to give the pyrimidine dithione derivatives 4a,b. The chloropyrimidines 3a,b were then methylated with methyl iodide to yield the methyl mercaptopyrimidines 5a,b. Following that , 4-mercapto-2-thiopyrimidine derivatives 6a,b were synthesized via a reaction between methyl mercaptopyrimidines 5a,b and thioura. Moreover, from 6a,b a series of thiopyrimidines derivatives 7a,b and 8a,b were synthesized. All compounds were screened against select microorganisms to assess their antimicrobial activity. Compounds 4b, 6a, and 8b showed the highest antibacterial activity among the synthesized derivatives . As a result, the three compounds were selected for a molecular docking study against the bacterial dihydropteroate synthase enzyme to which they revealed a good binding affinity.