Synthesis, antibacterial activity of 2,4-disubstituted oxazoles and thiazoles as bioisosteres

Two series of 2-substituted aryl, heteroaryl and alkyl, 4-substituted aryl 1,3-oxazole (2a-k) and thiazole (4a-k) molecular scaffolds containing divalent bioisosteres, viz., oxygen and sulphur were synthesized by condensing substituted amides and thioamides with substituted phenacyl bromide in absolute ethanol medium. The structure of newly synthesized compounds was characterized by analytical and spectral (IR, 1H-NMR, 13C-NMR and LC-MS) methods. The synthesized compounds were evaluated for qualitative (zone of inhibition) and quantitative antibacterial activity (MIC) by agar cup plate and micro-titration methods, respectively. Preliminary pharmacological observations revealed that some of the substituents such as 2-alkyl and heteroaryl at second position, chloro and bromo at the fourth position of the aryl moiety and a divalent sulphur atom in the five-membered heterocyclic ring system influenced significantly the antibacterial activity when compared to its bioisostere counterpart 2-substituted aryl, heteroaryl and alkyl, 4-substituted aryl 1,3-oxazole systems. © 2009 Bentham Science Publishers Ltd.