Synthesis and anthelmintic activity of some novel (E)-2-methyl/propyl-4-(2-(substitutedbenzylidene)hydrazinyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines

A series of some novel (E)-2-methyl/propyl-4-[(2-(substitutedbenzylidene)hydrazinyl]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines was synthesized and characterized by adopting an appropriate synthetic scheme. The effect of electron withdrawing and electron donating groups at the aromatic ring in presence of methyl and propyl substituents at the 2-position of the scaffold was evaluated for anthelmintic activity against adult Indian earthworms (Pheretima posthuma). Among 2-methyl-thieno[2,3-d]pyrimidine analogs, compounds with electron donating methoxy group either atpara-position or atmetaandpara-positions of the aromatic ring showed potent anthelmintic activity at 100 mu g/ml (284 and 261.8 mu M concentrations) for compounds5gand5hwith a mean paralytic time of 2.32, 2.22 min, and helminthicidal time of 22.38, 19.43 min, respectively. In contrast, the presence of electron withdrawing chloro group atorthoandpara-position of the aromatic ring was found to be favorable for the anthelminthic activity of the compounds5nand5o(at concentration of 259.7 mu M) with propyl group at the 2-position of the thieno[2,3-d]pyrimidine scaffold, exhibiting mean paralytic time of 2.5 min, 2.81 min and helminthicidal time of 21, 20.03 min, respectively. Anthelmintic activities of these four compounds5g,5h,5n, and5o(at the concentrations of 284, 261.8, 259.7, and 259.7 mu M, respectively) were found to be on par with the standard drug piperazine adipate (time for paralysis and death at 6.25 and 24.5 min, respectively) at concentration of 100 mu g/ml (431.03 mu M). Overall, the potency of these compounds (5g,5h,5n, and5o) is better than standard drug as they exhibited the same activity at 259.7-284 mu M as that of a standard drug (which has shown the same activity at 431.03 mu M). Further, the predicted ADME properties of all the synthesized compounds were found to be in the satisfactory ranges as predicted by SwissADME software and found to have drug-like properties. Thus, further modification of these compounds might lead to the discovery of more potent analogs.