一种新的三嗪类抗锥虫药:SIPI-1029及其类似物的合成和抗原虫作用

SYNTHESIS AND ANTIPROTOZOAL ACTIVITIES OF SOME NEW TRIAZINE DERIVATIVES INCLUDING A NEW ANTITRYPANOSOMALAGENT:SIPI-1029

摘要: 合成了1,2-二氢-2,2-二甲基-4,6-二氨基-1-(ω-卤代烷氧基)-s-三嗪类和O,O’-双(4,6-二氨基-1,2-二氢-2,2-二取付-s-三嗪-1-基)烷烃二醇两类化合物,它们大多有较好的体内抗疟原虫(Plasmodium berghei)作用,化合物IIc～e对用伊氏锥虫(Trypanosoma evansi)感染的小鼠,有较好的作用,经深入的药理、毒理和药代动力学以及疗效等研究,化合物IIe(SIPI-1029,T-46)被证明是一高效、低毒并有较长的血药半衰期的抗锥虫新药。

Abstract: Two series of compound:1,2-dihydro-2,2-dirnethyl-4,6-diamino-1-(ω-haloakyloxy)-s-triazines and O,O'-bis(4,6-diamino-1,2-dihydro-2,2-disubstituted-s-triazin-1-yl)alkanediols were synthesised and tested against Plasmodium berghei and Trypanosoma evansi in mice.Most title compounds showed good antimalarial activity and compounds IIc～eshowed good antitrypanosomal effect.After further studies on pharmacology,toxicology,pharmacokinetics and efficacy on infected cattles compound IIe(SIPI-1029,T-46)was shown to be a new highly active antitrypanosomal agent with low toxicity and long half life in plasma.