Sorafenib and its tosylate salt: a multikinase inhibitor for treating cancer

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, C₂₁H₁₆ClF₃N₄O₃, (I), and as a tosylate salt, 4‐(4‐{3‐4‐chloro‐3‐(trifluoromethyl)phenyl]ureido}phenoxy)‐2‐(N‐methylcarbamoyl)pyridinium 4‐methylbenzenesulfonate, C₂₁H₁₇ClF₃N₄O₃⁺·C₇H₇O₃S^?, (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.