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.

目前未知Covid-19的有效治疗方法。加上SARS-COV-2小说的冠状病毒的高度传染性，这有可能使全球医疗保健系统造成巨大而持久的负担，并为安全重新开放社会而努力。抗疟疾氯喹已被确定为一种药物，在某些情况下可能会重新使用以治疗Covid-19，这要归功于证据可以用来治疗其他冠状病毒，例如SARS-COV。然而，作为一种再利用药物，氯喹从未被优化以影响冠状病毒感染。因此，很有可能有更好的类似物来抗病毒指示。为了期望对基于喹啉的小分子支架的潜在应用在Covid-19及其症状的治疗中的潜在应用中，我们建议开发一个化学库的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Waverly Pharma合作进行，并将其Canam Bioresearch（已建立的药物化学合同研究组织）进行。通过学术研究实验室与专门从事临床上重要的小分子商业生产的工业合作伙伴之间的牢固和清晰的对话，我们将能够立即针对适用的分子支架，并开发一条治疗候选者的渠道，以进行未来研究。另一个重点是新的合成制剂，这可能有助于减轻现有的供应链的压力，以生产氯喹和羟基氯喹。