Maleate salts of bedaquiline

Acta Crystallographica Section E: Crystallographic Communications

Kari L. Clase¹  Mercy Okezue¹  Dale K. Purcell²  Matthias Zeller³  Stephen R. Byrn⁴  Daniel T. Smith⁴  Pamela Smith⁵  Susan Bogdanowich-Knipp⁶ 

[1] Biotechnology Innovation and Regulatory Science Center, Lilly Hall of Life Sciences, 915 State Street, Purdue University, West Lafayette, IN 47906, USA;Chemical Microscopy LLC, 1281 Win Hentschel Blvd., West Lafayette, IN 47906, USA;Department of Chemistry, Purdue University, 560 Oval Dr., W. Lafayette, IN 47907-2084, USA;Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall, West Lafayette, IN 47906, USA;Leading with Smart Science LLC, 5315 Shootingstar Ln, West Lafayette, IN 47906, USA;Ravine Pharmaceuticals LLC, 3425 DuBois St., West Lafayette, IN 47906, USA;

关键词: bedaquiline;    drug-resistant tuberculosis;    isomorphous organic salts;    desolvation;    crystal structure;   

DOI  :  10.1107/S2056989021002991

来源: DOAJ

【 摘 要 】

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl]dimethylazanium 3-carboxyprop-2-enoate}, C32H32BrN2O2+·C4H3O4−, namely, a hemihydrate, a tetrahydrofuran (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydromaleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intramolecular hydrogen bond typical for cis-dicarboxylic acid anions. The conformations of the cations and packing interactions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.

【 授权许可】

Unknown