ABSTRACT
Several synthetic routes of nirmatrelvir (the ingredient of a new drug to treat COVID-19 made by Pfizer) have been reported. We focused on a second route to improve the synthetic method of nirmatrelvir with a methodology that included different steps. The first step was an analysis of reaction byproducts using acetonitrile as a solvent of the condensation reaction to improve the inversion rate. Then, we used isobutyl acetate as a crystalline solvent to obtain the key intermediate as a solvate, which was a stable crystal product with high purity. Complementarily, we also used trifluoroacetic anhydride as the primary-amide dehydrating agent, and 2-methyl tetrahydrofuran as the solvent to prepare nirmatrelvir, which led to an overall yield of 48% via four steps and a purity of 99.5% according to high-performance liquid chromatography. We also investigated the crystal form of nirmatrelvir: the single-crystal features and transformation from a crystal form to nirmatrelvir were dependent upon temperature. Our data have great value for study of the synthetic method and crystal stability of nirmatrelvir. © 2023 The Royal Society of Chemistry.
ABSTRACT
Novel Schiff base was synthesized from the condensation reaction of metformin with [4-(Diethylamino) benzaldehyde (NBM). Different metal complexes were prepared using Pd (II), Pt (II), Cu (II), and V (IV) metal ions. All complexes showed the nonelectrolytic behavior. So, the expected molecular formulas for complexes were [Pd (NBM)Cl2], [Pt (NBM)Cl2], [Cu (NBM)2Cl2] and [VO (NBM)2]. The cytotoxicity of (NBM) Schiff base and its metal complexes on human cancer cell line, MCF-7, was investigated. V (IV) and Cu (II) complexes showed potential blood glucose lowering effect higher than the commercial metformin drug. VO (II) complex has superior antioxidant activity more than the other synthesized compounds and the standard ascorbic acid. Molecular docking investigation proved the presence of interesting interactions between all synthesized compounds with the active site amino acids of EGFR tyrosine kinase (anticancer activity). The molecular docking of metal complexes has observed effective inhibition for the specific mTOR protein that is expected to aid the growth of the COVID-19 virus. © 2022 John Wiley & Sons, Ltd.