title: Sorafenib and its tosylate salt: a multikinase inhibitor for treating cancer.
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.
authors.affiliation: Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad 500 007, India. sshiya@yahoo.com
authors.forename: K
authors.initials: K
authors.lastname: Ravikumar
authors.forename: B
authors.initials: B
authors.lastname: Sridhar
authors.forename: A K S
authors.initials: AK
authors.lastname: Bhujanga Rao
authors.forename: M
authors.initials: M
authors.lastname: Pulla Reddy
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use*; D000077157:Sorafenib; D014105:Tosyl Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D004791:Enzyme Inhibitors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014105:Tosyl Compounds; D009536:Niacinamide; D000077157:Sorafenib