Comparison of the crystal structures of the potent anticancer and anti-angiogenic agent regorafenib and its monohydrate.

Regorafenib {systematic name: 4-[4-({[4-chloro-3-(trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2-carboxamide}, C21H15ClF4N4O3, 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, C21H15ClF4N4O3·H2O. 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, R4(2)(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.

[Crystal structure and crystal form stability of trelagliptin succinate].

In order to investigate trelagliptin succinate's stability in solution, recrystallization and suspension methods in polar solvent (mainly in water and 95% alcohol) were used to study the crystal form transformation of trelagliptin succinate. Single crystal X-ray diffraction, powder X-ray diffraction and thermalgravimetric analysis, and differential scanning calorimetry were used to characterize the structure of the solid state form before and after transformation. The results showed that trelagliptin succinate can easily convert to trelagliptin hemi-succinate mediated by solvent, especially by polar solvent, namely trelagliptin hemi-succinate is more stable than trelagliptin succinate in solution.

Crystal structures of vortioxetine and its methanol monosolvate.

Vortioxetine, C18H22N2S, (1), systematic name 1-{2-[(2,4-di-methyl-phen-yl)sulfan-yl]phen-yl}piperazine, a new drug used to treat patients with major depressive disorder, has been crystallized as the free base and its methanol monosolvate, C18H22N2S·CH3OH, (2). In both structures, the vortioxetine mol-ecules have similar conformations: in (1), the dihedral angle between the aromatic rings is 80.04 (16)° and in (2) it is 84.94 (13)°. The C-S-C bond angle in (1) is 102.76 (14)° and the corresponding angle in (2) is 103.41 (11)°. The piperazine ring adopts a chair conformation with the exocyclic N-C bond in a pseudo-equatorial orientation in both structures. No directional inter-actions beyond normal van der Waals contacts could be identified in the crystal of (1), whereas in (2), the vortioxetine and methanol mol-ecules are linked by N-H⋯O and O-H⋯N hydrogen bonds, generating [001] chains.

Quetiapine N-oxide-fumaric acid (2/1).

THE TITLE COMPOUND (SYSTEMATIC NAME: 2-{2-[4-(dibenzo[b,f][1,4]thia-zepin-11-yl)piperazin-1-yl 1-oxide]eth-oxy}ethanol-fumaric acid (2/1)), C(21)H(25)N(3)O(3)S·0.5C(4)H(4)O(4), is one of the oxidation products of quetiapine hemifumaric acid. In the tricyclic fragment, the central thia-zepine ring displays a boat conformation and the benzene rings are inclined to each other at a dihedral angle of 72.0 (2)°. The piperazine ring adopts a chair conformation with its eth-oxy-ethanol side chain oriented equatorially. In addition to the main mol-ecule, the asymmetric unit contains one-half mol-ecule of fumaric acid, the complete mol-ecule being generated by inversion symmetry. In the crystal, O-H⋯O hydrogen bonds link the components into corrugated layers parallel to bc plane.

Moxifloxacinium chloride monohydrate.

The title compound {systematic name: 7-[(1S,6S)-8-aza-2-azonia-bicyclo-[4.3.0]non-8-yl]-1-cyclo-propyl-6-fluoro-8-meth-oxy-4-oxo-1,4-dihydro-quinoline-3-carb-oxy-lic acid chloride monohydrate}, C(21)H(25)FN(3)O(4) (+)·Cl(-)·H(2)O, crystallizes with two moxi-floxa-cinium cations, two chloride ions and two uncoordinated water mol-ecules in the unit cell. The crystal structure has a pseudo-inversion center except for the chloride ions. In both moxi-floxa-cinium cations, the quinoline rings are approximately planar, the maximum atomic deviations being 0.107 (3) and 0.118 (3) Å. The piperidine rings adopt a chair conformation while the pyrrolidine rings display a half-chair conformation. In the crystal, the carboxyl groups, the protonated piperidyl groups, the uncoordinated water mol-ecule and chloride anions participate in O-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonding; weak inter-molecular C-H⋯O and C-H⋯Cl hydrogen bonding is also present in the crystal structure.

Eprosartan mesylate, an angiotensin II receptor antagonist.

The title compound, eprosartan mesylate {systematic name: 2-butyl-1-(4-carb-oxy-benz-yl)-5-[(E)-2-carb-oxy-3-(thio-phen-2-yl)prop-1-en-yl]-1H-imidazol-3-ium methane-sulfonate}, C(23)H(25)N(2)O(4)S(+)·CH(3)O(3)S(-), one of the angiotensin II-receptor antagonists, is effective in regulating hypertension, induced or exacerbated by angiotensin II, and in the treatment of congestive heart failure, renal failure and glaucoma. In the eprosartan residue, which appears in this crystal in the cationic imidazolium form, the benzene ring plane is almost orthogonal to that of the imidazole ring, making a dihedral angle of 87.89 (2)°. The thio-phene ring forms dihedral angles of 66.54 (2) and 67.12 (2)° with the benzene and imidazole rings, respectively. The imidazolium NH group and the H atom of the aromatic carboxyl group participate in hydrogen bonds with the the O atoms of the anion, thus forming centrosymmetric aggregates made up of two cations and two anions each. The second carboxyl group further links the above-mentioned aggregates through a conventional centrosymmetric hydrogen-bonding motif into infinite chains along [011].