Synthesis And NA Activity Of 5-acetyl-2-Aminothiazole Derivatives

In recent years,the 5-acetyl thiazole derivatives have been made great development in the field of pesticides and medicine for their good biological activity.In order to find more potent agents against influenza viruses,two series of 5-acetyl-2-aminothiazole derivatives were designed,synthesized and evaluated for their inhibitory activities against neuraminidase of influenza H1N1 virus.,.The key intermediate 2-(5-acetyl-4-methylthiazol-2-amino)-4-thiazolone(4)was obtained from acetyl acetone via bromination,cyclization,chloride acetylation and molecular rearrangement reaction with thiocyanate.Then 5-subbenzyl-2-(5acetyl-4-methylthiazole)-4-thiazoline(5a～5q)were synthesized via Aldol condensation of intermediate 4 with corresponding aromatic aldehyde.All of compounds 5 were confirmed by 1H NMR,13C NMR and EI-MS.The neuraminidase inhibitory activities(A/PR/8/34(H1N1))of the target compounds were investigated at the concentration of 40 μg/mL.The results indicated that most of compounds 5 exhibited moderate to strong inhibitory activity,and the IC50(μg/mL)values of the most potent compounds 5a,5c,5e and 5g were 6.8 μg/mL,7.4 μg/mL,7.1 μg/mL and 7.5 μg/mL,respectively.N-(5-Acetyl-4-methylthiazole-2-base)acetamide/acrylamide(6a～6m)were synthesized from 4-methyl-5-acetyl-2-aminothiazole(2)via chloride acetylation(propionylation)and nucleophilic substitution.All of compounds 6 were confirmed by 1H NMR,13C NMR and EI-MS.Their neuraminidase inhibitory activities were investigated at the concentration of 40 μg/mL.The results indicated that most of compounds 6 exhibited moderate to strong inhibitory activity,and the IC50(μg/mL)values of the most potent compounds 6b,6i and 6m were 18.3 μg/mL,19.4 μg/mL and 15.1 μg/mL,respectively.