title: 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.
abstract: 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.
authors.affiliation: National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Ukrainets
authors.affiliation: SSI `Institute for Single Crystals' NAS of Ukraine, 60 Nauki ave., Kharkiv 61001, Ukraine.
authors.forename: Svitlana V
authors.initials: SV
authors.lastname: Shishkina
authors.affiliation: SSI `Institute for Single Crystals' NAS of Ukraine, 60 Nauki ave., Kharkiv 61001, Ukraine.
authors.forename: Vyacheslav N
authors.initials: VN
authors.lastname: Baumer
authors.affiliation: National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Gorokhova
authors.affiliation: National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine.
authors.forename: Lidiya A
authors.initials: LA
authors.lastname: Petrushova
authors.affiliation: Far Eastern State Medical University, 35 Murav'ev-Amursky St., Khabarovsk 680000, Russian Federation.
authors.forename: Galina
authors.initials: G
authors.lastname: Sim
mesh_terms: D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D003460:Crystallization; D018360:Crystallography, X-Ray; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D010146:Pain / Q000188:drug therapy; D051381:Rats; D013237:Stereoisomerism; D013843:Thiazines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C000606503:1,2-benzothiazine; D000700:Analgesics; D013843:Thiazines
keywords: 2λ6,1-benzothiazine-3-carboxamide; analgesic activity; antinociceptive activity; chiral crystals; crystal structure; pharmaceutical compound; pharmacological study