Novel pyrimidine-1,3,4-oxadiazole hybrids and their precursors as potential antimycobacterial agents.

Molecular hybridization and isostery are proven approaches in medicinal chemistry, and as such we used them to design novel compounds that we investigated as potential antimycobacterials to combat drug-resistant strains. Prepared -alkyl-2-(pyrimidine-5-carbonyl)hydrazine-1-carboxamides were cyclized to -alkyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amines along with their analogues. A total of 48 compounds were tested against  HRv, and , with oxadiazoles and C-C alkyls being the most effective from a concentration of 2 μM. Multidrug-resistant strains were inhibited at same concentrations as the susceptible strain. For the most potent -dodecyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amine, the mechanism of action related to cell wall biosynthesis was investigated. Pyrimidine-1,3,4-oxadiazole hybrids are unique antimycobacterial agents inhibiting mainly  strains without cross-resistance to current drugs and are thus promising drug candidates.