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

生产氯喹类似物和前体的合成库，用于立即和未来开发 COVID-19 治疗

• 批准号: 552044-2020
• 负责人: Herbert, David
• 金额: $ 3.64万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=703502
• 关键词: Production; Synthetic; Library; Chloroquine; Analogs

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.

目前尚不清楚COVID-19的有效治疗方法。再加上导致COVID-19的SARS-CoV-2新型冠状病毒的高传染性，这可能会给地球仪的医疗系统带来巨大而持久的负担，并阻碍安全地重新开放社会的努力。抗疟疾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，这要归功于它可用于治疗其他冠状病毒（如SARS-CoV）的证据。然而，作为一种重新利用的药物，氯喹从未被优化以影响冠状病毒感染;因此，很可能有一种更好的类似物用于抗病毒适应症。基于对喹啉类小分子支架在治疗COVID-19及其症状中的潜在应用的预期，我们建议开发氯喹衍生物和前体衍生物的化学库。该项目将与商业药物开发组织韦弗利制药公司和已建立的药物化学合同研究组织CanAm生物研究公司合作进行。通过学术研究实验室与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的清晰对话，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。另一个重点是新型合成制剂，可能有助于减轻现有氯喹和羟氯喹生产供应链的压力。