Tripathi M, Verma M, Palit G, Shanker K
Department of Pharmacology and Therapeutics, King George's Medical College, Lucknow, India.
Arzneimittelforschung. 1993 Oct;43(10):1045-9.
1-(N-Antipyrinylglycyl)-3-arylideneamino)-2-thiobarbituric acids (III) were synthesized from 1-arylidene-4-(N-antipyrinyl glycyl)-3-thiosemicarbazones (II). Compounds II in turn were prepared from 4-amino antipyrine. Compounds III were finally converted into 1-(N-antipyrinylglycyl)-3-[(3'-chloro-4-aryl)azitidinyl]-2-t hiobarbituric acids (IV). 4-Aminoantipyrine was also treated with different N-protected amino acids in the presence of N,N'-dicyclohexylcarbodiimide to yield N-(antipyrinylcarbamoyl) substituted alkyl benzamides (V); their debenzoylation yielded 2-(amino-N-antipyrinyl) substituted acetamides (VI). The compounds were screened for their antidepressant activity. Compounds IIId, Va and Vb exhibited activity better than imipramine with less toxicity (ALD50 > 1000 mg/kg).
1-（N-安替比林基甘氨酰基）-3-亚芳基氨基）-2-硫代巴比妥酸（III）由1-亚芳基-4-（N-安替比林基甘氨酰基）-3-硫代氨基脲（II）合成。化合物II又由4-氨基安替比林制备。化合物III最终转化为1-（N-安替比林基甘氨酰基）-3-[(3'-氯-4-芳基)氮杂环丁烷基]-2-硫代巴比妥酸（IV）。4-氨基安替比林还在N,N'-二环己基碳二亚胺存在下与不同的N-保护氨基酸反应，生成N-（安替比林基氨基甲酰基）取代的烷基苯甲酰胺（V）；它们的脱苯甲酰基反应生成2-（氨基-N-安替比林基）取代的乙酰胺（VI）。对这些化合物进行了抗抑郁活性筛选。化合物IIId、Va和Vb表现出比丙咪嗪更好的活性且毒性更小（半数致死量>1000mg/kg）。
