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    • 7. 发明公开
    • Use of nitrogen-containing compounds as antiparasitics, and compositions containing them
    • 使用含氮化合物作为抗菌剂,以及含有它们的组合物
    • EP0355279A3
    • 1992-07-08
    • EP89109658.8
    • 1989-05-29
    • DRUG & VACCINE DEVELOPMENT CORPORATION
    • Henderson, Graeme B.Ulrich, Peter C.Cerami, Anthony
    • A61K31/175A61K31/345A61K31/00A61K31/495C07D307/71C07C281/10C07C281/18C07C337/08
    • A61K31/175A61K31/00A61K31/345A61K31/495Y02A50/409Y02A50/414Y02A50/415
    • The present invention relates to the treatment of diseases caused by invading organisms in a host by first identifying an enzymatic difference between the host and the invading organism and then administering to the host a pharmaceutically effective amount of a subversive substrate for the differing enzyme of the invading organism, whereby the action of the differing enzyme causes a result counter to the intended result and function of the enzyme that results in its debilitation or death. In particular, treatment of parasitic diseases caused by kinetoplastids including trypanosomes and leishmanias, e.g., African sleeping sickness, Chagas' disease, oriental sore and kala-azar is accomplished by administration of a pharmaceutically effective antiparasitic amount of a competitive toxigenic substrate for trypanothione reductase. Methods of treatment and compositions therefor lcontain a competitive toxigenic substrate for trypanothione reductase. Numerous compounds and corresponding compositions are disclosed.
    • 本发明涉及通过首先鉴定宿主与入侵生物体之间的酶差异,然后向宿主施用药学有效量的侵入性不同酶的颠覆性底物来治疗宿主入侵生物引起的疾病 由此不同酶的作用导致与预期的导致其衰弱或死亡的酶的预期结果和功能相反的结果。 特别是,通过给予药学上有效的抗寄生虫剂量的针对锥虫硫代还原酶的竞争性产毒底物来实现由包括锥虫和利什曼原虫在内的动物造成的寄生虫病,例如非洲睡眠病,恰加斯病,东方疮和卡拉 - 沙ar的治疗。 化合物选自结构式为R 1 C(X)= NNHC(= Z)NHR 2(I)的化合物,其中R 1 = H或低级烷基X =可还原的 芳族体系或可还原芳烷基Z = O,S或NHR 2 = H或下式的烷基氨基烷基:其中n为1至6的整数,R 3和R 3为 4独立地是低级烷基或一起形成含有1至2个杂原子的环烷基或杂环基的一部分,其中至少一个是氮; 并且所述杂原子中的第二个选自氮,氧和硫; 条件是当杂环的第二个杂原子是氮并形成哌嗪环时,它可以任选被与哌嗪环的第一氮上的化合物部分相同的取代基取代。 或者,当R 3为低级烷基时,R 4可以是R 1 C(X)= NNHC(= Z)NH(CH 2)n - 的第二组,其中R 1,X ,Z和n具有如上所定义的值,而所述第二组R 4与已经连接至带有第一组R 4的氮的基团相同。 X的环系可以选自许多醌类和杂环或杂环变体。