Synthesis of Substituted Pyrazoles from Aryl-sydnones.

BACKGROUND: In this current work, a new synthesis strategy was developed to obtain 1,3,4-trisubstituted pyrazoles derivatives. METHODS: A series of 1,3,4-trisubstituted pyrazoles have been prepared via 1,3-dipolar cycloaddition reaction of 3-phenylsydnones with a variety of alkenes derivatives, symmetric and non-symmetric alkynes derivatives, N-phenyl-maleimide, N-benzylmaleimides, and maleic anhydride under conventional manner. RESULTS: Moreover, in this work, it has been demonstrated that the 4-bromopyrazole intermediates can be further functionalized by a combination of Suzuki-Miyaura crosscoupling reactions with aryl-boronic acids and N-arylation reactions of anilines. CONCLUSION: In summary, we have developed a new method to obtain 1,3,4 triarylated pyrazoles through 3-phenylsydnone 1,3-dipolar cycloadditions. By comparing the different reactions, it is apparent that high temperatures and xylene as solvent are key to achieving pyrazoles derivatives. The best yields were observed for symmetric and non-symmetric alkynes as dipolarophiles.

Synthesis of new heterocyclic compounds based on pyrazolopyridine scaffold and evaluation of their neuroprotective potential in MPP+-induced neurodegeneration.

Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP+-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP+-induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 µM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways.

3-Methyl-sulfanyl-5-phenyl-1,2,4-triazine.

In the mol-ecule of the title compound, C10H9N3S, the dihedral angle between the triazine and phenyl rings is 11.77 (7)°. In the crystal, mol-ecules are linked by π-π stacking inter-actions [centroid-centroid distances = 3.7359 (3) and 3.7944 (4) Å], forming layers parallel to the bc plane.

3,4,6-Trimethyl-1-phenyl-1H-pyrazolo-[3,4-b]pyridine.

In the title compound, C(15)H(15)N(3), the 1H-pyrazolo-[3,4-b]pyridine system and the phenyl ring are each individually planar, with r.m.s. deviations of 0.017 (2) and 0.011 (2) Å, respectively; the dihedral angle between the two aromatic systems is 9.33 (10)°. The crystal packing is stabilized by offset π-π stacking between parallel pyrazolo-[3,4-b]pyridine ring systems [face-to-face distance = 3.449 (6) Å].