A new solvate of afatinib, a specific inhibitor of the ErbB family of tyrosine kinases
| Autor: | Gabriel Lima Barros de Araujo, Trev Parker, Amrinder Singh Rai, Matthias Zeller, Stephen R. Byrn |
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| Rok vydání: | 2017 |
| Předmět: |
crystal structure
Stereochemistry pseudo-inversion center 02 engineering and technology Crystal structure 010403 inorganic & nuclear chemistry 01 natural sciences Research Communications ErbB tyrosine kinase inhibitor Turn (biochemistry) chemistry.chemical_compound pseudo-symmetry Amide Quinazoline General Materials Science Crystallography Hydrogen bond Chemistry Free base General Chemistry hydrogen bonding 021001 nanoscience & nanotechnology Condensed Matter Physics 0104 chemical sciences Solvent QD901-999 Amine gas treating 0210 nano-technology |
| Zdroj: | Acta Crystallographica Section E: Crystallographic Communications Acta Crystallographica Section E: Crystallographic Communications, Vol 73, Iss 3, Pp 417-422 (2017) |
| ISSN: | 2056-9890 |
| Popis: | The water/acetonitrile solvent of afatinib exhibits pseudo-inversion symmetry. Exact inversion symmetry is broken by swapping of oxygen and CH2 moieties of its tetrahydrofuranyl substituents, which can be traced back to C—H⋯N and C—H⋯O interactions of the acetonitrile solvent molecules with the tetrahydrofuranyl units. Afatinib (systematic name: N-{4-(3-chloro-4-fluoroanilino)-7-[(tetrahydrofuran-3-yl)oxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide), is a specific inhibitor of the ErbB family of tyrosine kinases. The free base form crystallizes from acetonitrile as a mixed water–acetonitrile solvent, C24H25ClFN5O3·0.25C2H3N·2H2O. It crystallizes with two independent molecules (A and B) in the asymmetric unit of the chiral space group P4212, but exhibits close to perfect pseudo-inversion symmetry, emulating P4/ncc that relates the two molecules to each other. Exact inversion symmetry is however broken by swapping of oxygen and CH2 moieties of the outer tetrahydrofuranyl substituents of the two independent molecules. This can, in turn, be traced back to C—H⋯N and C—H⋯O interactions of the acetonitrile solvent molecules with the tetrahydrofuran oxygen and CH2 units. In the crystal, neighboring molecules are connected via N—H⋯O hydrogen bonds between the secondary amine and the amide keto O atom. Additional hydrogen bonds are formed through the water solvent molecules, which are engaged in O—H⋯O and O—H⋯N hydrogen bonds connecting to the dimethylamino N atom, the amide keto O atom, and one of the quinazoline N atoms of a neighboring molecule, leading to an intricate three-dimensional hydrogen-bonded superstructure. There are two types of channels stretching along the direction of the c axis; one along the fourfold rotational axis, occupied by acetonitrile solvent molecules situated on that axis, and parallel channels which are not occupied by any solvent. |
| Databáze: | OpenAIRE |
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