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Comparison of the crystal structures of the potent anticancer and anti-angiogenic agent regorafenib and its monohydrate.
- Source :
- Acta Crystallographica Section C: Structural Chemistry; Apr2016, Vol. 72 Issue 4, p291-296, 5p
- Publication Year :
- 2016
-
Abstract
- Regorafenib {systematic name: 4-[4-({[4-chloro-3-(trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2-carboxamide}, C<subscript>21</subscript>H<subscript>15</subscript>ClF<subscript>4</subscript>N<subscript>4</subscript>O<subscript>3</subscript>, is a potent anticancer and anti-angiogenic agent that possesses various activities on the VEGFR, PDGFR, raf and/or flt-3 kinase signaling molecules. The compound has been crystallized as polymorphic form I and as the monohydrate, C<subscript>21</subscript>H<subscript>15</subscript>ClF<subscript>4</subscript>N<subscript>4</subscript>O<subscript>3</subscript>·H<subscript>2</subscript>O. The regorafenib molecule consists of biarylurea and pyridine-2-carboxamide units linked by an ether group. A comparison of both forms shows that they differ in the relative orientation of the biarylurea and pyridine-2-carboxamide units, due to different rotations around the ether group, as measured by the C-O-C bond angles [119.5 (3)° in regorafenib and 116.10 (15)° in the monohydrate]. Meanwhile, the conformational differences are reflected in different hydrogen-bond networks. Polymorphic form I contains two intermolecular N-H...O hydrogen bonds, which link the regorafenib molecules into an infinite molecular chain along the b axis. In the monohydrate, the presence of the solvent water molecule results in more abundant hydrogen bonds. The water molecules act as donors and acceptors, forming N-H...O and O-H...O hydrogen-bond interactions. Thus, R<subscript>4</subscript><superscript>2</superscript>(28) ring motifs are formed, which are fused to form continuous spiral ring motifs along the a axis. The (trifluoromethyl)phenyl rings protrude on the outside of these motifs and interdigitate with those of adjacent ring motifs, thereby forming columns populated by halogen atoms. [ABSTRACT FROM AUTHOR]
- Subjects :
- REGORAFENIB
CRYSTAL structure
VASCULAR endothelial growth factor receptors
Subjects
Details
- Language :
- English
- ISSN :
- 20532296
- Volume :
- 72
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Acta Crystallographica Section C: Structural Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 114438735
- Full Text :
- https://doi.org/10.1107/S2053229616003727