2- 胺基 - 苯駢 [e][1,3]-4- 酮衍生物合成及中樞神經系統活性之研究
Synthesis of 2-Amino-Benzo[e][1,3]thiazin-4-ones Derivatives and Studies of Their Central Nervous System Activities
中文摘要
本論文乃在探討2-胺基-苯駢[e][1,3]-4-酮化合物衍生物合成方法。以2-甲硫基-苯駢[e]
[1,3]-4-酮做為起始物，以不同胺基化合物進行取代反應，胺基化合物包括氨水、丁胺、
辛基胺、羥胺、3-氨基-1-丙醇、乙二胺、二甲縮醛胺、氮,氮-二甲基乙二胺、三乙胺、呱啶、二乙二胺 氮-乙基-二乙二胺、1,4-氧氮六圜、2-甲醇-咯烷、苯胺和對乙氧基苯胺等。反應在室溫中進行，
以甲醇為溶媒，經6-48 小時之後，即可得到各式產物。所得產物經再結晶純化後，由熔點測定、
紅外線、質譜儀分析、核磁共振等光譜分析，判定其結構為2-胺基-苯駢[e][1,3]-4-酮類 化合物，產率約在60~90%。
將製備的2-胺基-苯駢[e][1,3]-4-酮化合物4、5、8、9、11 和 14 分別送測中樞神經藥理 活性評估，在麩胺酸受體及γ-胺基丁酸受體藥理實驗中，發現對於麩胺酸受體結合能力，化合 物9 及 14 分別為 20.09%和 19.06%的抑制作用比對照組 5,5-二氫內醯臆甘醇醯
5.10%為佳。對 γ-胺基丁酸-A 受體接受器[3H]muscimol 結合抑制作用中，化合物 9 抑制 作用為28.41%比對照組苯妥因 4.35%為佳，然而化合物 5 和 8 卻呈現相反作用，抑制作用分 別為-10.89%和-15.84%。而正值數值越高，表示與受體結合能力越強，將來可以繼續研究化 合物屬於致效劑或拮抗劑；而負值的意義可能因受體蛋白質結構改變而造成的結果。
英文摘要
A facile synthesis of 2-amino-benzo[e][1,3]thiazin-4-one derivatives
was achieved. A methanolic solution of 2-methylsulfanyl-benzo[e][1,3] thizin-4- one was treated with various amine compounds at 25℃. The amine compounds are ammonia water, n-butylamine, n-octylamine, hydroxylamine, 3-
aminopropanol, ethylenediamine, N,N-dimethylethyl- enediamine,
aminoacetaldehyde dimethylacetal, triethylamine, piperidine, piperazine, N- ethylpiperazine, morpholine, (S)-(+)-2-methanol- pyrrolidine, aniline, and p- phenetidine. The reaction completed in 6 to 48 hours, and the recrystallized products were identified with melting point measurement, IR, MS, 1H and 13C nuclear magnetic resonance spectroscopic analyses. The yields were between 60 to 90%.
Initially, six analogues including 4, 5, 8, 9, 11 and 14 were submitted for central nervous system activity assay by using glutamate receptor and gamma-
aminobutylamine receptor binding inhibition methods. The glutamate receptor binding inhibition method showed that compounds 9 and 14 demonstrated 20.09% and 19.06% were more active than that 5,5-dihydro-hydantoin demonstrated 5.10%. On the other hand, in the gamma-aminobutylamine-A
receptor [3H]muscimol binding assay showed that compound 9 demonstrated 28.41% was more active than that dilantin demonstrated 4.35%. Compounds 5 and 8 were the other action to the gamma-aminobutylamine-A receptor
[3H]muscimol binding assay that demonstrated —10.89% and —15.84%.
