Abstract |
Sorafenib, a drug that targets malignant cancer cells and cuts off the blood supply feeding the tumour, has been crystallized as the free base, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N-methylpyridine-2-carboxamide, C(21)H(16)ClF(3)N(4)O(3), (I), and as a tosylate salt, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl)pyridinium 4-methylbenzenesulfonate, C(21)H(17)ClF(3)N(4)O(3)(+)·C(7) H(7)O(3)S(-), (II). In both structures, the sorafenib molecule is in an extended conformation. The pyridine-2-carboxamide group exhibits a syn conformation of the N atoms in (I), whereas an almost anti orientation is present in (II). In both crystal structures, the two terminal groups, viz. pyridine-2-carboxamide and the trifluorophenyl ring, are oriented differently to the conformations found in enzyme-bound sorafenib. The sorafenib molecules in (I) are linked into zigzag chains by N-H···O hydrogen bonds, whereas in (II) the presence of the additional tosylate anion results in the formation of chains of fused hydrogen-bonded rings. This study reveals the variations in the solid-state conformation of the sorafenib molecule in different crystalline environments.
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Authors | K Ravikumar, B Sridhar, A K S Bhujanga Rao, M Pulla Reddy |
Journal | Acta crystallographica. Section C, Crystal structure communications
(Acta Crystallogr C)
Vol. 67
Issue Pt 1
Pg. o29-32
(Jan 2011)
ISSN: 1600-5759 [Electronic] United States |
PMID | 21206080
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Benzenesulfonates
- Enzyme Inhibitors
- Phenylurea Compounds
- Protein Kinase Inhibitors
- Pyridines
- Tosyl Compounds
- Niacinamide
- Sorafenib
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Topics |
- Antineoplastic Agents
(chemistry, therapeutic use)
- Benzenesulfonates
(chemistry, pharmacology, therapeutic use)
- Crystallography, X-Ray
- Enzyme Inhibitors
(chemistry, pharmacology, therapeutic use)
- Humans
- Hydrogen Bonding
- Molecular Conformation
- Molecular Structure
- Neoplasms
(drug therapy)
- Niacinamide
(analogs & derivatives)
- Phenylurea Compounds
- Protein Kinase Inhibitors
(chemistry, therapeutic use)
- Pyridines
(chemistry, pharmacology, therapeutic use)
- Sorafenib
- Tosyl Compounds
(chemistry, pharmacology)
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