Design, synthesis and evaluation of novel thienopyrimidine-based agents bearing diaryl urea functionality as potential inhibitors of angiogenesis.

Inhibition of angiogenesis is a promising strategy for the treatment of cancer. Herein, we describe the design and synthesis of thieno[2,3-d]pyrimidine-1,3,4-thiadiazole-aryl urea derivatives 11a-m to evaluate their efficacy in the chick chorioallantoic membrane (CAM) assay. Among target agents, 11i had a considerable activity against prostate cancer cell line, PC3 (IC50 = 3.6 µM). Moreover, induction of apoptosis, good inhibitory activity against the growth of capillary blood vessels, and inhibition of VEGFR-2 phosphorylation were noticeable parameters which convinced us that 11i could be considered as a promising candidate for the discovery of novel drugs to treat tumors, particularly prostate cancer.

(E)-N'-(3,3-Diphenyl-allyl-idene)-p-toluene-sulfonohydrazide.

In the title compound, C(22)H(20)N(2)O(2)S, the mol-ecule adopts a twisted E configuration around the C=N bond. The two phenyl rings are twisted from each other, making a dihedral angle of 78.00 (12)°. The methyl-substituted benzene ring makes dihedral angles of 32.37 (14) and 69.70 (12)° with the two phenyl rings. In the crystal structure, mol-ecules are linked into extended chains along the b axis through inter-molecular N-H⋯O hydrogen bonds.

Synthesis of alpha-oximinoketones under ultrasound irradiation.

The reaction of 6-acylmethylphenanthridines with isoamyl nitrite results alpha-oximino-6-acylmethylphenanthridines in 73-95% yields in DMF under ultrasound irradiation. Compared with conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction time and higher yields.

(E)-N'-Benzyl-idene-p-toluene-sulfono-hydrazide.

In the title compound, C(14)H(14)N(2)O(2)S, a novel sulfonamide derivative, an intra-molecular C-H⋯O hydrogen bond generates an S(5) ring motif. The mol-ecule adopts a twisted E configuration around the C=N bond. An inter-molecular N-H⋯O hydrogen bond generates an R(2) (2)(8) ring motif. The dihedral angle between the rings is 85.37 (9)°. The H atoms of the methyl group have rotational disorder with refined site occupancies of ca 0.63/0.37. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link neighbouring mol-ecules into dimers which stack along the a axis with a centroid-centroid distance of 3.8856 (10) Å.

Solvatochromic, spectroscopic and DFT studies of a novel synthesized dye: l-(4-Dimethylaminophenyl)-2-(5H-phenanthridine-6-ylidene)-ethanone (6-KMPT).

A novel solvatochromic l-(4-dimethylaminophenyl)-2-(5H-phenanthridine-6-ylidene)-ethanone (6-KMPT) dye was synthesized and characterized by means of NMR, IR, mass spectroscopies. Also, it was studied using UV-vis and fluorescence spectroscopic methods in a broad range of solvents. UV-vis results showed that increasing 6-KMPT concentration dose not cause molecular aggregation in chloroform. Varying the temperature in the range from 25 to 55 degrees C dose not have a significant effect on the characteristics bands of the molecule. However, in the presence of surfactant SDS the UV-vis spectrum undergoes drastic alteration. This phenomenon is related to the removal of hydrogen atom from nitrogen atom of phenanthridine moiety. Fluorescence spectroscopic results showed that 6-KMPT has an appreciable fluorescence quantum yield. The effect of excitation wavelength, concentration of 6-KMPT, concentration of oxygen and surfactants (SDS, C(16)TAB, CPC, Brij-35) were studied. Further results showed that the fluorescent behavior of 6-KMPT can be attributed to planarity induced by intramolecular hydrogen bonding which can in turn be destroyed by anionic surfactant SDS. Results showed that oxygen and SDS can be operate as fluorescence quencher compounds for 6-KMPT and Stern-Volmer plot showed a straight line. Fluorescence polarization and anisotropy of 6-KMPT in chloroform strongly depend on concentration. The 6-KMPT exhibits solvent-induced spectral band shifts. By using Lippert equation, the change of dipole moment of 6-KMPT molecule upon excitation was estimated as 6.39 D. Furthermore, absorption, fluorescence emission, Stokes shift values and fluorescence quantum yield (Phi(F)) of 6-KMPT in different solvents of polarity were determined. Maximum Phi(F) value of 0.372 for 6-KMPT molecule was found in ethanol solvent with a Stokes shift of 2446.8 cm(-1). The results of DFT calculations showed that tautomer 2c (enol) energetically is more stable than tautomer 2b (keto) in gas phase whereas it was vice versa in CHCl(3).

Ultrasound-assisted synthesis of aromatic 1,2-diketones from oximinoketones under neutral conditions in aqueous media.

We report a convenient, neutral, and facile methodology for the synthesis of aromatic 1,2-diketones from the corresponding oximinoketones in the presence of I2/SDS/water system under ultrasound-assisted conditions. Furthermore, a series of compounds were synthesized and characterized by melting point, IR, NMR, MS, and elemental analysis. Utilization of easy reaction conditions, very high to excellent yields, and short reaction times makes this manipulation potentially very useful.