Synthesis of 2,4-disubstituted thiazoles and selenazoles as potential antifilarial and antitumor agents. 2. 2-Arylamido and 2-alkylamido derivatives of 2-amino-4-(isothiocyanatomethyl)thiazole and 2-amino-4-(isothiocyanatomethyl)selenazole
摘要:
The synthesis of a series of 2-arylamido and 2-alkylamido derivatives of 2-amino-4-(isothio-cyanatomethyl)thiazole and 2-amino-4-(isothiocyanatomethyl)selenazo is described. In vitro antiproliferative evaluations were carried out using L1210 cells. The 2-(alkylamido)thiazole derivatives were moderately antiproliferative, with IC50's of 4-8 mu M. A significant increase in activity was obtained for the arylamido derivatives, with IC50's of 0.2-1 mu M. The results obtained for the selenazoles were similar to those for the thiazoles. 2-Benzamido-4-(isothiocyanatomethyl)thiazole (19) was found to be a potent inhibitor of GMP synthetase. None of the compounds prepared in this study demonstrated antifilarial activity.
通过涉及2-氨基-4-(氯甲基)噻唑(1)和2-氨基-4-的化学转化制备了4-(异硫氰酸根合甲基)噻唑-2-氨基甲酸甲酯和4-(异硫氰酸根合甲基)硒唑-2-氨基甲酸甲酯(氯甲基)硒唑(2)分别作为起始原料。由(2-氨基噻唑-4-基)乙酸制备高类似物的4-(2-异硫氰酸根合乙基)噻唑-2-氨基甲酸甲酯。评价所有制备的化合物抑制白血病L1210细胞增殖的能力。4-(异硫氰酸根合甲基)噻唑-2-氨基甲酸甲酯(7)是该筛选中活性最高的化合物,其IC50 = 3.2 microM抑制了L1210白血病细胞的生长。有丝分裂阻断似乎是其细胞毒性活性的主要机制。化合物7也是唯一对实验感染的寄生虫表现出显着的体内抗丝虫活性的化合物。该化合物以100 mg / kg x 5天的剂量对彭氏布鲁氏菌无活性。