Advancement of antiviral inhibitors of chikungunya virus

项目总结 迫切需要治疗基孔肯雅病毒(CHIKV)感染的新疗法来解决 这种病原体在整个美洲的传播令人震惊。我们已经确定了三个不同的系列有效的， CHIKV复制的选择性和口服生物利用型抑制剂。在这项第二期更新SBIR项目中，我们将 将这些CHIKV抑制剂系列优化到开发前阶段并推出首个CHIKV抗病毒药物 IND支持研究的候选人。为了完成这项任务，我们将进行综合药物化学 优化/生物概况活动，以优化每种药物的效力、类药物特性和口腔暴露 系列片。将确定一名或多名开发前候选人，并通过候选人选择提拔候选人 大鼠和犬非GLP重复给药毒性的研究。

PROJECT SUMMARY Novel therapies for the treatment of chikungunya virus (CHIKV) infections are urgently needed to address the alarming spread of this pathogen across the Americas. We have identified three distinct series of potent, selective, and orally bioavailable inhibitors of CHIKV replication. In this Phase II renewal SBIR project, we will optimize these series of CHIKV inhibitors to Pre-Development stage and advance a first ever CHIKV antiviral candidate to IND-enabling studies. To accomplish this task, we will execute an integrated medicinal chemistry optimization/biological profiling campaign to optimize the potency, drug-like properties and oral exposure of each series. One or more Pre-Development Candidates will be identified and advanced through candidate selection studies into non-GLP repeat-dose tox in both rats and dogs.