Two pseudo-enantiomeric forms of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ(6),1-benzothiazine-3-carboxamide and their analgesic properties

• Published in: Acta crystallographica. Section C, Structural chemistry Structural chemistry, 2016-05, Vol.72 (Pt 5), p.411-415
• Main Authors: Ukrainets, Igor V, Shishkina, Svitlana V, Baumer, Vyacheslav N, Gorokhova, Olga V, Petrushova, Lidiya A, Sim, Galina
• Format: Article
• Language: English
• Subjects: Analgesics - chemistry; Analgesics - pharmacology; Animals; Crystallization; Crystallography, X-Ray; Male; Models, Molecular; Molecular Conformation; Pain - drug therapy; Rats; Stereoisomerism; Thiazines - chemistry; Thiazines - pharmacology
• ISSN: 2053-2296
• DOI: 10.1107/S2053229616005453

The fact that molecular crystals exist as different polymorphic modifications and the identification of as many polymorphs as possible are important considerations for the pharmaceutic industry. The molecule of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ(6),1-benzothiazine-3-carboxamide, C17H16N2O4S, does not contain a stereogenic atom, but intramolecular hydrogen-bonding interactions engender enantiomeric chiral conformations as a labile racemic mixture. The title compound crystallized in a solvent-dependent single chiral conformation within one of two conformationally polymorphic P212121 orthorhombic chiral crystals (denoted forms A and B). Each of these pseudo-enantiomorphic crystals contains one of two pseudo-enantiomeric diastereomers. Form A was obtained from methylene chloride and form B can be crystallized from N,N-dimethylformamide, ethanol, ethyl acetate or xylene. Pharmacological studies with solid-particulate suspensions have shown that crystalline form A exhibits an almost fourfold higher antinociceptive activity compared to form B.