抗血吸虫病新药S72014及其同系物的合成

抗血吸虫病新药S72014,1-(5-硝基-2-噻唑)-3-二异丁氨基甲基-四氢咪唑酮-2及其同系物,系以硝唑咪为原料,与相应的第二胺及甲醛用曼氏反应合成。S72014和它的绝大多数同系物对小白鼠、兔及猴体内的日本血吸虫都有显著的杀灭作用。S72014对小白鼠的毒性比硝唑咪低达10倍,其化疗指数则高达硝唑咪的3.5倍。用小白鼠进行的S72014与硝唑咪对化学惊厥药物影响的实验表明,S72014在剂量大于硝唑咪引起惊厥的剂量10倍时,没有影响。本文还略论了S72014和它的同系物的构效关系。

SYNTHESIS OF A NEW SCHISTOSOMICIDE S72014 AND ITS HOMOLOGS

A new antischistosomal agent (S72014), 1-(5-nitro-2-thiazolyl)-3-diisobutylami—nomethyl-2-imidazolidinone, and its homologs were synthesized by using niridazole as. starting material and appropriate secondary amines through Mannich reaction. S72014. was shown to possess pronounced antischistosomal activity in animals (mice, rabbits, dogs and monkeys) infected with Schistosoma japonicum. S72014 was 10 times less toxic than niridazole and had a chemotherapeutic index 3.5 times as great. Comparative combination tests of S72014 and niridazole with chemical convulsants in mice showed that S72014 did not produce seizure at a dose as high as ten times that of niridazole which would cause epileptic convulsion significantly. Structure-activity relationship was discussed.