Advancement to Clinical Candidate of Novel, Potent and Selective Chikungunya virus inhibitor series

 描述(由申请人提供)：迫切需要治疗基孔肯雅病毒(CHIKV)感染的新疗法，以应对这种病原体在美洲令人震惊的传播。我们已经确定了一系列有效的、选择性的、口服生物可用的CHIKV复制抑制剂。在这个直接到阶段的项目中，我们将优化这一系列 CHIKV抑制剂进入开发前阶段，并将有史以来第一个CHIKV抗病毒候选药物推向IND使能研究。为了完成这项任务，我们将实施一项整合的药物化学优化/生物图谱活动，以优化该系列的效力、类药物特性和口腔暴露。一个或多个Pre-Development候选药物将通过对大鼠和狗的非GLP重复剂量毒素的候选筛选研究来确定和晋级。

 DESCRIPTION (provided by applicant): 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 a series of potent, selective, and orally bioavailable inhibitors of CHIKV replication. In this Direct to Phase project, we will optimize this 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 the 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.