The identification of a new series of growth inhibitors of Trypanosoma cruzi, the causative agent of Chagas' disease, is described. In vitro screening of a subset of compounds from our in-house compound collection against the parasite led to the identification of hit compound 1 with low micromolar inhibition of T. cruzi growth. SAR exploration on the hit compound led to the identification of compounds that show nanomolar parasite growth inhibition (T. cruzi EC50 ≤ 100 nM) and no cytotoxicity in human cells (HeLa CC50 > 50 μM). Further investigation identified CYP51 inhibition (compound 11 CYP51 IC50 52 nM) as a possible mechanism of action of this new class of anti-parasitic agents.

中文翻译：

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发现4-（（1-（1H-咪唑-2-基）烷氧基）甲基）吡啶是新型的克鲁氏锥虫生长抑制剂。

描述了查格氏锥虫（Chagas's病的病原体）的新系列生长抑制剂的鉴定。从我们内部的化合物库中对寄生虫进行化合物的子集的体外筛选，导致鉴定出对克氏锥虫生长具有低微摩尔抑制作用的命中化合物1。SAR探索了这种受打击的化合物，从而鉴定出显示出纳摩尔级寄生虫生长抑制作用（T. cruzi EC50≤100 nM）且对人细胞无细胞毒性（HeLa CC50> 50μM）的化合物。进一步的研究确定CYP51抑制（化合物11 CYP51 IC50 52 nM）是这种新型抗寄生虫药的可能作用机理。