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

点击翻译按钮获取中文摘要

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.