Tecovirimat-Related Substance: Characterization, Hirshfeld Analysis, Theoretical Study, In Silico Toxicity Assessment

Crystal structures of 4- (trifluoromethyl) benzene-1-carbohydrazide (1), 4- (trifluoromethyl) -N’-4- (trifluoromethyl) phenylcarbonylbenzohydrazide (2) and (1R, 2S, 6R, 7S, 8S, 10R) -4- (4- (trifluoromethyl) phenylcarbonylamino) -4-azatetracyclo 5. 3. 2. 08, 10. 02, 6dodec-11-ene-3, 5-dione (3) were first reported. Besides the three new single-crystal structures, the single-crystal structure of tecovirimat (4) was also described herein. Hirshfeld analysis quantified intermolecular interactions, and PXRD confirmed high crystal phase purity. DSC data and packing energy calculations demonstrated that the melting point order matched the magnitude of packing energies for compounds with similar structures and analogous intermolecular interactions. According to the ICH M7 guidelines, in silico genotoxicity assessment using Derek Nexus and Sarah Nexus indicated that 2 showed no structural alerts for genotoxicity (ICH M7 Class 5), whereas 1 and 3 were classified as ICH M7 Class 3 due to structural features associated with potential genotoxicity, warranting further experimental evaluation.