Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements.

Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured.

Arylureas derived from colchicine: Enhancement of colchicine oncogene downregulation activity.

Our efforts to get therapeutically useful colchicine derivatives for the treatment of cancer have led us to synthetize and biologically evaluate twenty-seven N,N'-disubstituted ureas containing a colchicine moiety and an aryl fragment. The cytotoxicity of the compounds, their ability to inhibit the expression of oncogenes related to telomerase activation and to the VEGF/VEGFR-2 autocrine process, such as c-MYC, hTERT and VEGF and their capability to downregulate c-MYC and VEGFR-2 proteins and the secretion of VEGF have been measured. In these biological evaluations, we have found that the change of the acetyl group in colchicines for an N-arylurea unit causes a great improvement in anticancer properties.

Design, synthesis and antimalarial evaluation of novel thiazole derivatives.

As part of our medicinal chemistry program's ongoing search for compounds with antimalarial activity, we prepared a series of thiazole analogs and conducted a SAR study analyzing their in vitro activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. The results indicate that modifications of the N-aryl amide group linked to the thiazole ring are the most significant in terms of in vitro antimalarial activity, leading to compounds with high antimalarial potency and low cytotoxicity in HepG2 cell lines. Furthermore, the observed SAR implies that non-bulky, electron-withdrawing groups are preferred at ortho position on the phenyl ring, whereas small atoms such as H or F are preferred at para position.

Design, synthesis, and biological evaluation of novel fluorinated ethanolamines.

The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane.

Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: synthesis and biological activity of fluorinated tebufenpyrad analogs.

The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity.

Synthesis of highly functionalised enantiopure bicyclo[3.2.1]- octane systems from carvone.

The commercially available monoterpene carvone has been efficiently converted into the tricyclo[3.2.1.

1H, 13C and 19F NMR spectroscopy of polyfluorinated ureas. Correlations involving NMR chemical shifts and electronic substituent effects.

Seventeen N-(mono-, di-, tri-, tetra- and penta-fluorophenyl)-N'-(3-nitrophenyl)ureas were prepared and characterized. Complete assignment of their (1)H, (13)C and (19)F NMR data was undertaken and the correlation of the chemical shifts of the ureido protons with field-inductive and mesomeric electronic substituent parameters was studied using the Swain-Lupton model. The best correlations were obtained when the study was limited to certain substitution patterns, e.

Preparation and promotion of fruit growth in kiwifruit of fluorinated N-phenyl-N'-1,2,3-thiadiazol-5-yl ureas.

Seventeen phenyl-fluorinated analogues of thidiazuron [N-phenyl-N'-(1,2,3-thiadiazol-5-yl)urea, TDZ] have been prepared and characterized. The effects of each fluorinated urea on growth and quality of kiwifruits (Actinidia deliciosa) were evaluated by comparison with untreated (control) and TDZ-treated fruits. The results obtained showed a clear dependence of the growth-promoting activity of these fluorinated ureas on the pattern and degree of fluorine substitution in the phenyl ring.