The development of nirmatrelvir 1 (the active agent in PAXLOVID) was undertaken using a “lightspeed” paradigm to develop an oral antiviral treatment for SARS-CoV-2 (COVID-19). This paper describes our chiral control strategy to deliver high-quality drug substances from first in human studies to an ICH Q3A aligned commercial filing over a period of 17 months. We illustrate our approach to modeling, targeted synthetic efforts, and analytical method development to measure the only two observed stereoisomers instead of the potential 63 in the final drug substance. This paper also provides an overview of how we employed the knowledge gained on chiral control from nirmatrelvir and applied it to our second-generation oral inhibitor, ibuzatrelvir 2.

中文翻译：

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为加速 COVID 计划构建和发展手性控制策略


nirmatrelvir 1（PAXLOVID 中的活性剂）的开发是使用“光速”范式进行的，以开发 SARS-CoV-2 （COVID-19） 的口服抗病毒治疗药物。本文介绍了我们的手性控制策略，可在 17 个月的时间内将高质量的原料药从首次人体研究交付到 ICH Q3A 一致的商业申报。我们说明了我们的建模方法、有针对性的合成工作和分析方法开发，以测量最终原料药中仅观察到的两种立体异构体，而不是潜在的 63 种立体异构体。本文还概述了我们如何利用从 nirmatrelvir 获得的手性控制知识并将其应用于我们的第二代口服抑制剂 ibuzatrelvir 2。