title: Tosylate salts of the anticancer drug lapatinib.
abstract: Two tosylate salts of an anticancer drug lapatinib, viz. a monotosylate [systematic name: ({5-[4-({3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)quinazolin-6-yl]furan-2-yl}methyl)[2-(methylsulfonyl)ethyl]azanium 4-methylbenzenesulfonate], C29H27ClFN4O4S(+)·C7H7O3S(-), (I), and a ditosylate [systematic name: 4-({3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)-6-]5-({[2-(methylsulfonyl)ethyl]azaniumyl}methyl)furan-2-yl[quinazolin-1-ium bis(4-methylbenzenesulfonate)], C29H28ClFN4O4S(2+)·2C7H7O3S(-), (II), were obtained during crystallization attempts for polymorphism. In both structures, the lapatinib cation is in a distorted U-like conformation and the tosylate anion is clamped between the aniline N atom and methylamine N atom through N-H···O hydrogen bonds, forming an R2(2)(15) ring motif. The 4-anilinoquinazoline ring system is essentially planar in (I), while it is twisted in (II), controlled by an intramolecular C-H···N interaction. In (I), alternating cations and anions are linked by N-H···O hydrogen bonds into C2(2)(6) chains. These chains are linked by cations in a helical manner. The presence of the additional tosylate anion in (II) results in the formation of one-dimensional tapes of fused hydrogen-bonded rings through N-H···O and C-H···O interactions. These studies augment our understanding of the role of nonbonded interactions in the solid state, which is useful for correlation to the physicochemical properties of drug products.
authors: Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors: K
authors: K
authors: Ravikumar
authors: B
authors: B
authors: Sridhar
authors: Jagadeesh Babu
authors: JB
authors: Nanubolu
authors: A K S
authors: AK
authors: Bhujanga Rao
authors: R
authors: R
authors: Jyothiprasad
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D000077341:Lapatinib; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology; D012492:Salts / Q000737:chemistry* / Q000494:pharmacology; D014105:Tosyl Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D012492:Salts; D014105:Tosyl Compounds; D000077341:Lapatinib
keywords: anticancer drug; crystal structure; hydrogen bonding; lapatinib; pharmaceuticals; tosylate salts