Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
Syngene International Ltd. , Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India.
J Med Chem. 2016 Nov 10;59(21):9890-9905. doi: 10.1021/acs.jmedchem.6b01265. Epub 2016 Oct 26.
Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγ mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.
在 2-氨基吡嗪系列的 5-苯基环上引入水溶性基团，发现了对恶性疟原虫（Plasmodium falciparum）血期具有高活性的化合物。几种化合物在两种不同的疟疾小鼠模型（感染伯氏疟原虫的小鼠和感染疟原虫的 NOD-scid IL-2Rγ小鼠）中表现出高体内疗效。其中一个先导化合物 3 还具有良好的药代动力学特性，并且对肝期和配子体期寄生虫也具有很强的活性。
