Synthesis And Biological Activity Of4-methyl-6-aryl-5-acetyl-2-amide-1,3-thiazine

The thiazine compounds are a class of heterocyclic compounds with biological activityand are also a kind of important chemical intermediates. Recent study shows that they have aprospect of application on antiinfluenza，antibacterial，antidiabetic and insecticide. Theresearch of the thiazine compounds has become a new hot spot. This paper designs a newsynthesis of thiazine compounds and tests their biological activity on the inhibitory activity ofNA in vitro，antidepressant activity and antitumor activity in vitro.1） Ten of new4-methyl-6-aryl-5-acetyl-2-amide-1,3-thiazines were designed andsynthesized. With aldehydes and acetyl acetone as material，sodium sulfuric acid as catalyst，after the night reaction of mixing，3-(arylmethylene)-2,4-pentanedione was obtained. Andthen with thiourea in refluxing in the ethanol，concentrated hydrochloric acid as the catalyst.4-methyl-6-aryl-5-acetyl-2-amino-1,3-thiazines were synthesized. Finally，4-methyl-6-aryl-5-acetyl-2-amino-1,3-thiazines were acetylated to give4-methyl-6-aryl-5-acetyl-2-amide-1,3-thiazine，the structure confirm by1HNMR.2）The4-methyl-6-aryl-5-acetyl-2-amino-1,3-thiazines were tested on the inhibitoryactivity of NA in vitro. The results indicated that some of the compounds had certainneuraminidase inhibition，in which3i inhibition rate reached59.17%，IC5039.12μg/mL. Thecompounds showed a good prospect of development and utilization.3）The4-methyl-6-aryl-5-acetyl-2-amino-1,3-thiazines were tested on antidepressant.The results showed that some of the compounds had certain antidepressant activity. The bestactivity of the compounds was3b. Inhibition rate of3b was41%. The compounds showed thevalue of futher optimization.4） For a comprehensive study of biological activity of4-methyl-6-aryl-5-acetyl-2-amide-1,3-thiazine compounds， antitumor activity was tested. By MTT method，4-methyl-6-aryl-5-acetyl-2-amino-1,3-thiazines and4-methyl-6-aryl-5-acetyl-2-acetylamino-1,3-thiazines were tested on antitumor activity in vitro. Experimental results indicated thatthe compounds showed good in vitro inhibition to A549cells，Hela cells and Bel7402cells.At the concentration of0.500μmol/mL，the inhibition rates of compound2a、2c、2d、2f、2g、3a、3b、3c、3d、3e、3f reached90%. Compound3f was the best one，whose inhibitionrate was97.6%. Even at the concentration of0.100μmol/mL，the inhibition rates ofcompound3b、3j、3c hovered50%. As for Bel7402cells，at the concentration of0.500μmol/mL，the inhibition rates of compound3b reached98%. Even at the concentration of0.100μmol/mL，the inhibition rates of compounds3b、3e also reached60%. As for Hela cells，at the concentration of0.500μmol/mL，the inhibition rates of compounds2a、2f、2g、2i reached90%. At the concentration of0.250μmol/mL，the inhibition rates of mostcompounds reached50%. The results was dealt with SPSS17software. The good activecompounds were furtuer studied by the cell morphology，Hochest/PI dyeing experiment. Thecompounds in cancer research indicated a good experiment effect.