A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC.
Background: Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) decreased mortality and hospital admissions in high-risk patients with mild to moderate COVID-19. Nevertheless, there is a lack of data about the pharmacoeconomic impact of these antivirals in the Omicron era. We conducted a pharmacoeconomic analysis assessing the medical costs of the use of these antivirals compared to those occurred in people who refused the treatment.
WHO declared the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus as a global pandemic (coronavirus disease 2019 (COVID-19)) in March 2020. Molnupiravir (MPV) is an oral antiviral drug that received use authorization for mild to moderate COVID-19 treatment in adults. However, the global and national drug testing and research of MPV is still difficult due to lack of standards and validated procedures.
Individuals with chronic liver or kidney disease are at increased risk of severe COVID-19. Molnupiravir is an orally administered antiviral authorized for the treatment of mild-to-moderate COVID-19 in adults at risk of progression to severe disease. Two nonrandomized, open-label, single-dose, multicenter, phase 1 trials were conducted to investigate the effects of hepatic and renal impairment on the tolerability and pharmacokinetics of molnupiravir (800 mg) and its metabolite β-D-N4-hydroxycytidine (NHC; NCT05386589/NCT05386758).
Molnupiravir (1) is one among the limited therapeutic options for treating COVID-19 infection and exhibits pan-antiviral potency. Because of urgent demands during the COVID-19 pandemic, a number of methods were developed to offer more efficient routes. In this report, we present a facile 2-step and scalable synthesis of molnupiravir for batch processing and show the implementation of continuous flow biocatalysis to improve the efficiency in synthesis.
Background: The US Food and Drug Administration (US FDA) granted emergency use authorization (EUA) for multiple coronavirus disease 2019 (COVID-19) drugs as a medical countermeasure during the COVID-19 pandemic. Despite these drugs' fast-track nature, concerns persist regarding their efficacy and potential adverse effects. Thus, the continuous surveillance and understanding of these drugs' safety profiles are crucial in such scenarios.
