Epalrestat tetrahydrofuran monosolvate: crystal structure and phase transition

Umeda, D; Putra, OD; Gunji, M; Fukuzawa, K; Yonemochi, E

Yonemochi, E (reprint author), Hoshi Univ, Sch Pharm & Pharmaceut Sci, 2-4-41 Ebara, Shinagawa, Tokyo 1458501, Japan.



The title compound, epalrestat {systematic name: (5Z)-5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidine-3-acetic acid}, crystallized as a tetrahydrofuran monosolvate, C15H13NO3S2 center dot C4H8O. Epalrestat, an important drug for diabetic neuropathy, has been reported to exist in polymphic, solvated and co-crystal forms. In the molecule reported here, the phenyl ring is inclined to the rhodamine ring by 22.31 (9)degrees, and the acetic acid group is almost normal to the rhodamine ring, making a dihedral angle of 88.66 (11)degrees. In the crystal, pairs of O-H center dot center dot center dot O hydrogen bonds are observed between the carboxylic acid groups of epalerstat molecules, forming inversion dimers with an R-2(2)(8) loop. The dimers are linked by pairs of C-H center dot center dot center dot O hydrogen bonds, forming chains along [101]. The solvate molecules are linked to the chain by a C-H center dot center dot center dot O(tetrahydrofuran) hydrogen bond. A combination of thermal analysis and powder X-ray diffraction revealed that title compound desolvated into epalerstat Form II. One C atom of the tetrahydrofuran solvate molecule is positionally disordered and has a refined occupancy ratio of 0.527 (18): 0.473 (18).

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