Pyridine and 3-methylpyridine solvates of the triple sulfa drug constitutent sulfamethazine

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• 作者：Urmila H. Patel and Ketankumar P. Purohit
• 关键词：pharmaceutical solvates ; sulfamethazine ; SMZ ; benzenesulfonamide ; crystal structure ; triple sulfa drug
• 刊名：Acta Crystallographica Section C
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：73
• 期：1
• 页码：9-12
• 全文大小：820K
• ISSN：1600-5759

文摘

Sulfonamides display a wide variety of pharmacological activities. Sulfamethazine [abbreviated as SMZ; systematic name 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide], one of the constitutents of the triple sulfa drugs, has wide clinical use. Pharmaceutical solvates are crystalline solids of active pharmaceutical ingredients (APIs) incorporating one or more solvent molecules in the crystal lattice, and these have received special attention, as the solvent molecule can impart characteristic physicochemical properties to APIs and solvates, therefore playing a significant role in drug development. The ability of SMZ to form solvates has been investigated. Both pyridine and 3-methylpyridine form solvates with SMZ in 1:1 molar ratios. The pyridine monosolvate, C₁₂H₁₄N₄O₂S·C₅H₅N, crystallizes in the orthorhombic space group Pna2₁, with Z = 8 and two molecules per assymetric unit, whereas the 3-methylpyridine monosolvate, C₁₂H₁₄N₄O₂S·C₆H₇N, crystallizes in the orthorhombic space group P2₁2₁2₁, with Z = 4. Crystal structure analysis reveals intramolecular N—H…N hydrogen bonds between the molecules of SMZ and the pyridine solvent molecules. The solvent molecules in both structures play an active part in strong intermolecular interactions, thereby contributing significantly to the stability of both structures. Three-dimensional hydrogen-bonding networks exist in both structures involving at least one sulfonyl O atom and the amine N atom. In the pyridine solvate, there is a short π–π interaction [centroid–centroid distance = 3.926 (3) Å] involving the centroids of the pyridine rings of two solvent molecules and a weak intermolecular C—H…π interaction also contributes to the stability of the crystal packing.