Crystal structure of 4-(benzofuran-2-yl)-2-(3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl)thiazole, C28H20FN3OS

Abstract C28H20FN3OS, triclinic, P1̅ (no. 2), a = 9.5719(5) Å, b = 10.7499(6) Å, c = 10.9238(5) Å, α = 95.470(4)°, β = 102.133(4)°, γ = 97.962(4)°, V = 1079.30(10) Å3, R gt(F) = 0.0482, wR ref(F 2) = 0.1143, T = 150(2) K.</jats:p

Reactions of organolithium reagents with quinazoline derivatives

This review deals with directed and regioselective lithiation of various quinazoline derivatives by the use of alkyllithiums in anhydrous THF at low temperature. Reactions of the lithium reagents obtained from the lithiation reactions with a range of electrophiles give the corresponding substituted derivatives in high yields. The procedures are simple, efficient and general to provide derivatives which might be difficult to produce by other means. In some cases nucleophilic addition of alkyllithiums takes place to produce the corresponding addition products via 1,2- and 3,4-additions. In other cases nucleophilic substitution or halogen-lithium exchange reactions occur

Crystal structure of 2-[4-(methylsulfanyl)quinazolin-2-yl]-1-phenylethanol

In the molecule of the title compound, C17H16N2OS, the almost planar methylsulfanylquinazoline group [the methyl C atom deviates by 0.032 (2) Å from the plane through the ring system] forms an interplanar angle of 76.26 (4)° with the plane of the phenyl group. An intramolecular O—H...N hydrogen bond is present between the quinazoline and hydroxy groups. In the crystal, molecules are stacked along the b-axis direction

Crystal structure of 2-(3-nitrophenyl)-1,3-thiazolo[4,5-b]pyridine

In the title compound, C12H7N3O2S, the dihedral angle between the planes of the thia­zolo­pyridine ring system (r.m.s. deviation = 0.005 Å) and the benzene ring is 3.94 (6)°. The nitro group is rotated by 7.6 (2)° from its attached ring. In the crystal, extensive aromatic [pi]-[pi] stacking [shortest centroid-centroid separation = 3.5295 (9) Å] links the mol­ecules into (001) sheets

Crystal structure of 2-[4-(methylsulfanyl)quinazolin-2-yl]-1-phenylethanol

In the mol­ecule of the title compound, C17H16N2OS, the almost planar methyl­sulfanylquinazoline group [the methyl C atom deviates by 0.032 (2) Å from the plane through the ring system] forms an inter­planar angle of 76.26 (4)° with the plane of the phenyl group. An intra­molecular O-H***N hydrogen bond is present between the quinazoline and hy­droxy groups. In the crystal, mol­ecules are stacked along the b-axis direction

Crystal structure of 2-cyclohexyl-1,3-thiazolo[4,5-b]pyridine

In the title compound, C12H14N2S, the cyclo­hexane ring adopts a chair conformation with the exocyclic C-C bond in an equatorial orientation. The mean plane through the cyclo­hexane ring (all atoms) is twisted from the thia­zolo­pyridine ring system (r.m.s. deviation = 0.013 Å) by 39.57 (6)°. In the crystal, mol­ecules form (100) sheets, although there are no specific directional inter­actions between them. The crystal stucture was refined as a two-component perfect twin

S-phase kinase protein 2 is an attractive therapeutic target in a subset of diffuse large B-cell lymphoma

S-phase kinase protein 2 (SKP2), an F-box protein, targets cell-cycle regulators including cycle-dependent kinase inhibitor p27KiP1 via ubiquitin-mediated degradation. SKP2 is frequently overexpressed in a variety of cancer cells and has been implicated in oncogenesis; however, its role in diffuse large B-cell lymphoma (DLBCL) has not been elucidated. Therefore, we investigated the role of SKP2 and its ubiquitin-proteasome pathway in a large series (301) of DLBCL patient samples and a panel of DLBCL cell lines. Using immunohistochemistry, SKP2 was detected in 41.6% of DLBCL tumours and was inversely associated with p27Kip1 protein level. The DLBCL subset with high SKP2 and low p27Kip1 showed a strong correlation with the proliferating index marker Ki-67 (p \u3c 0.0001) and also with the germinal centre phenotype (p = 0.0147). Treatment of DLBCL cell lines with bortezomib or expression of SKP2-specific siRNA causes down-regulation of SKP2 and accumulation of p27Kip1, leading to suppression of growth by inducing apoptosis. Furthermore, treatment of DLBCL cells with bortezomib causes apoptosis via involving the mitochondrial pathway and activation of caspases. Finally, treatment of DLBCL cells with bortezomib down-regulated the expression of XIAP, cIAP1, and survivin. Altogether, these results suggest that SKP2 and the ubiquitin-proteasome pathway may be a potential target for therapeutic intervention in DLBCL