Synthesis of novel azole functionalized trifluoromethyl pyrido[2,3-d] pyrimidinone derivatives and their antimicrobial activity

Abstract

Novel azole functionalized pyrido[2,3-d] pyrimidinone derivatives 6a-l were prepared starting from 2-Amino- 6-(thiophen-2-yl)-4-(trifluoromethyl)nicotinonitrile 1 reacting with trifluoroacetic acid in the presence of conc. H2SO4 and further reaction with bromoethyl acetate to obtain 3a and 3b. Compounds 3a and 3b further reacted with hydrazine hydrate to afford hydrazide compounds 4a and 4b. Compounds 4a and 4b on treating with phenylisothiocyanate give compound 5a and b. Compound 5a and 5b on reaction with different reagents (NaOH, H2SO4 and N2H4.H2O) produced different azole-substituted (triazolothione, thiadiazole, triazole) functionalized trifluoromethyl pyrido[2,3-d] pyrimidinone derivatives 6a-l respectively. All the products 6a–l were screened against gram +ve, gram –ve bacteria and fungal strains. Compounds 6ad showed promising activity against Bacillus subtilis microbial-type culture collection (MTCC) 121 at <25.6 micromolar concentration. Promising compounds were further screened for minimum bactericidal concentration against B. subtilis MTCC 121 using ciprofloxacin as standard reference and found to show very good activity. These compounds also screened for biofilm inhibition activity against B. subtilis MTCC 121 using erythromycin as standard confirming the high activity.