Antimicrobial investigations on synthetic p-tolylazo derivatives of thienopyrimidinone based on an ortho funtionalized thiophene nucleus

Abstract

New derivatives of thieno[2,3-d]pyrimidin-4-one, 4a-c, and 6 were respectively synthezised based on thiophene derivative, 2c,ortho-disposed amino and ester groups. Carbohydrazide, bearing 7, was obtained by hydrazinolysis of 3-ethoxycabonylmethyl derivative, 4c. Compounds 4b and 7 were used to build up two series of novel 3-substituted-methylthieno[2,3-d]pyrimidin-4-ones, 7-11, and their corresponding 3-substituted-amino analogues 12, 15a,b, 18, which were of significant interest for biological study. The new thieno[2,3-d]pyrimidin-4-one derivatives, with various groups in position 3, were screened for their preliminary antimicrobial activity against a representative panel of Gram-positive and Gram-negative bacteria as well as fungi strains. The compounds tested displayed different levels of antibacterial and antifungal effects, with the assays carried out on six pathogenic bacteria and six pathogenic fungi. Of these compounds, the 3-unsubstituted-thieno[2,3-d]pyrimidin-4(3H)-one, 4a, showed the lowest effect on pathogenic bacteria, while the corresponding 3-substituted analogues produced inhibitory effects against bacteria similar or superior to the reference drug Tetracycline. For those derivatives of thieno[2,3-d]pyrimidin-4-one in which the 3-position contains a methylene moiety, it has been observed that the antibacterial effect was in general found to be significantly higher than the corresponding analogues with a substituted-amino moiety in position 3. Despite promising in vitro antibacterial activity of the new thienopyrimidin-4-ones, only compounds 7, 10 and 11, among the compounds tested, exhibited some kind of antifungal activity. The detailed synthesis and biological screening data were reported.