Structural analysis and properties of two novel pharmaceutical salts of letermovir

• Published in: Journal of molecular structure 2023-07, Vol.1284, p.135414, Article 135414
• Main Authors: Chai, Yuzhu, Shen, Jianwei, Cai, Zhuoer, Hua, Xiu-Ni, Zhao, Jinhong, Xu, Dan, Zhu, Chunxia, Sun, Baiwang
• Format: Article
• Language: English
• Subjects: Letermovir; Novel pharmaceutical
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135414

•Two novel pharmaceutical salts of letermovir (LM) were successfully achieved.•This is the first report of a single crystal structure of LM, which could contribute to the development of corresponding drugs.•Salt 1 and salt 2 showed better solubility and stability under wet conditions, and had the potential to replace the bulk drug. Two novel pharmaceutical salts of letermovir (LM) were successfully achieved by a slow reaction in solution containing LM with ethylenediamine (EDA) and diisopropylamine (DIPA). In this article, crystal structure, X-ray diffraction, thermal properties, 1H NMR, 13C NMR, HPLC analysis, stability and solubility of salt 1 and salt 2 have been discussed. Salt 1 crystalized in R3 space group and salt 2 crystalized in P3221 space group. The formation of salt was proved by pKa rule and single crystal determination. From the perspective of crystal structure, for salt 1 and salt 2, the strong hydrogen bond makes the crystal structure more stable. The weak interaction between molecules is further studied by Hirshfeld surface and 2D-fingerprint plots. Notably, this is the first report of a single crystal structure of LM, which could contribute to the development of corresponding drugs. In addition, salt 1 and salt 2 showed better solubility and stability under wet conditions, and had the potential to replace the bulk drug. Two novel pharmaceutical salts of letermovir (LM) were successfully synthesized. [Display omitted]