Anionic Favipiravir in Salt-type Cocrystals with Monoethanolamine and Ethylenediamine

Favipiravir (FVR) is an antiviral medication used to treat influenza in Japan (Fig. 1). It is also being studied to treat a number of other viral infections. Like experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.1 It is, however, only indicated for novel influenza (strains that cause more severe disease), rather than seasonal influenza. The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase.2 The possible tautomerism of FVR has been investigated computationally.3 It was found that the enol-like form was substantially more stable in aqueous solution than the keto-like form, meaning that FVR likely exists almost exclusively in the enol-like form in aqueous solution (Fig. 2). An enol form of FVR was found in the crystal structure of FVR.4 The crystal structure of FVR has been analyzed in silico research for structural analysis of FVR and its activity against COVID-19.5,6 It was found that four tautomeric structures could be considered to be ligands obtained by density functional theory (DFT) calculations. The crystal structures of the cocrystals of many organic compounds with neutral FVR are already known,6,7 but an anionic form of FVR similar to that studied in this work has not yet been known. This is for the first time obtained and crystallographic studied as an anionic form of FVR, which has been obtained using a basic co-former as monoethanolamine (MEA) and ethylendiamine (en). The given results can be used to describe the interaction of FVR with the amino acids of a protein molecule. The purpose of this paper is to study the effects of the salt formation of FVR with the basic molecules MEA and en on its geometric parameters and its conformation. Salts of FVR with MEA (1) and en (2) were prepared by a similar procedure: (1): the reaction of FVR (0.1 mM, 0.157 mg) and MEA (0.1 mM, 6.11 mg), and (2): the reaction of FVR (0.1 mM, 6.11 mg) and en (0.1 mM, 6.01 mg), which were dissolved in ethanol (10 mL). The reaction mixtures were stirred for 15 min at a temperature of ∼60°C. Both crystals were obtained by slow evaporation of the reaction solutions at the room temperature. The hydrogen atoms of the amino groups in both structures were located on a difference-Fourier map, but other hydrogen 2022 © The Japan Society for Analytical Chemistry