Synthesis and biological evaluation of 1,3,4-oxadiazole bearing dihydropyrimidines as potential antitubercular agents

A series of 5-(4-acetyl-5-(aryl)-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-(2-fluorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-ones (4a-l) were synthesized in very good yields (56-78 %). Biginelli adduct 1 synthesized in the first step was reacted with hydrazine hydrate to furnish carbohydrazide intermediate 2 which on further reaction with different aryl aldehydes yielded 4-(2-fluorophenyl)-6-methyl-N'-(aryl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carbohydrazides (3a-l). These intermediates 3a-l were cyclized with the help of acetic anhydride to give the titled compounds 4a-l. All the newly synthesized compounds 4a-l were screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv (Mtb) using Lowenstein-Jensen method. Compounds 4c, 4f, 4h, 4i and 4j inhibited more than 90 % of mycobacterial growth. Minimum inhibitory concentration (MIC) for compound 4i was found to be equipotent (MIC: 0.20 mu g/ml) to the reference drug isoniazid. Structure activity relationship revealed that the presence of electron withdrawing group/atoms at para position of phenyl ring remarkably enhanced the antitubercular activity of synthesized compounds.