Synthess and anti-proliferative activity in vitro of new 5-(2-amino-3-pyridyl)-2-thioxo-3H-1,3,4-oxadiazolederivatives

摘要

The reaction of 2-aminonicotinic acid hydrazide 1 with carbon disulfide gives 5-(2-amino-3-pyridyl)-2-thioxo-3H-1,3,4-oxadiazole 4 which on treatment with ethyl bromoacetate affords 5-(2-amino-3-pyridyl)-2-ethoxycarbonylthio-1,3,4-oxadiazole 5.Treatment of compound 5 with the appropriate primary and secondary amines provided the corresponding oxadiazole derivatives:alkyl-(cycloalkyl-,aryl)-aminocarbamylmthylthio- 6-10 or alkyl-(cycloalkyl-,aryl)-amino-11-16.The reaction of 5 with benzylamine furnishes two products:5-(2-amino-3-pyridyl)-2-benzylamino-1,3,4-oxadiazole 18 and di(benzylcarbamylmehtyl) surfide 19.Selected compounds are tested for their antiproliferative activity in vitro.One of them 19 reveals cytotoxc activity against the cells of 4 human tumor cell lines applied.the ID50 valuesare in the range of the international activity criterion for synthetic agents(4 mug/ml).