Production of a Synthetic Library of Chloroquine Analogs and Precursors for Immediate and Future Development of COVID-19 Treatments

目前尚不清楚COVID-19的有效治疗方法。再加上导致COVID-19的新型冠状病毒SARS-CoV-2的高度传染性，这可能会给全球卫生保健系统带来巨大而持久的负担，并阻碍安全重新开放社会的努力。抗疟疾药物氯喹已被确定为在某些情况下可能被重新用于治疗COVID-19的药物，因为有证据表明它可用于治疗其他冠状病毒，如sars冠状病毒。然而，作为一种重新利用的药物，氯喹从未被优化用于治疗冠状病毒感染；因此，很可能有更好的类似物用于抗病毒适应症。基于喹啉类小分子支架在治疗COVID-19及其症状中的潜在应用，我们建议建立一个氯喹衍生物和前体衍生物的化学文库。该项目将与商业药物开发机构Waverly Pharma和已建立的药物化学合同研究机构CanAm biresearch合作进行。通过学术研究实验室和专门从事临床重要小分子商业化生产的工业合作伙伴之间强有力而明确的对话，我们将能够针对立即适用的分子支架，并为未来的研究开发治疗候选药物。另一个重点是可能有助于减轻现有氯喹和羟氯喹生产供应链压力的新型合成制剂。

Effective treatments for COVID-19 are presently unknown. Combined with the highly contagious nature of the SARS-CoV-2 novel coronavirus responsible for causing COVID-19, this threatens to place an enormous and persistent burden on healthcare systems across the globe, and hamper efforts to safely reopen society. The anti-malarial chloroquine has been identified as a drug that might be repurposed to treat COVID-19 in some cases, thanks to evidence it can be used to treat other coronaviruses such as SARS-CoV. As a repurposed drug, however, chloroquine was never optimized to affect coronavirus infection; it is therefore highly likely that a better analogue is possible for an antiviral indication. In anticipation of developing interest in the potential application of quinoline-based small molecule scaffolds in the treatment of COVID-19 and its symptoms, we propose to develop a chemical library of chloroquine derivatives and precursor derivatives. This project will be undertaken in partnership with Waverly Pharma, a commercial drug development organization, and CanAm Bioresearch, an established medicinal chemistry contract research organization. Through robust and clear dialogue between an academic research lab and an industrial partner specializing in the commercial production of clinically important small molecules, we will be able to target both immediately applicable molecular scaffolds and develop a pipeline of therapeutic candidates for future study. An additional focus is on novel synthetic preparations that may help alleviate pressures on existing supply chains for the production of chloroquine and hydroxychloroquine.