Second generation benzofuranone ring substituted noscapine analogs: synthesis and biological evaluation.

Microtubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems.

Adenine-based acyclic nucleotides as novel P2X3 receptor ligands.

A new series of acyclic nucleotides based on the adenine skeleton and bearing in 9-position a phosphorylated four carbon chain has been synthesized. Various substituents were introduced in 2-position of the adenine core. The new compounds were evaluated on rat P2X3 receptors, using patch clamp recording from HEK transfected cells and the full P2X3 agonist alpha,beta-meATP as reference compound.

Adenosine A2A receptor antagonists: new 8-substituted 9-ethyladenines as tools for in vivo rat models of Parkinson's disease.

A new series of 8-substituted 9-ethyladenine derivatives has been synthesized and tested at rat and human adenosine receptors. Binding data demonstrates that some compounds could represent new tools suitable for in vivo studies in rat models of Parkinson's disease and for the design of new molecules with improved affinity and selectivity at human AA(2A)R.Clinical evidence has demonstrated that AA(2A)R antagonists could be an alternative approach to the treatment of Parkinson's disease.

Synthesis and biological activity of trisubstituted adenines as A 2A adenosine receptor antagonists.

The discovery of new drugs for the treatment of neurodegenerative disorders, such as Parkinson's disease, has become an attractive field of research. Due to the regulation of D(2) receptor activity by A(2A) adenosine receptor, potent and selective ligands of A(2A) subtype could be useful tools to study neurodegenerative disorders. A series of 2,8-disubstituted-9-ethyladenine derivatives was synthesized and tested in binding affinity assay at human adenosine receptors.

Synthesis and stability studies of 2',3',5'-tri-O-acetyl-2-amino(-N6-cyclopentyl)-1-deazaadenosines.

In this article, we report on the synthesis of 2',3',5'-tri-O-acetyl-2-amino-1-deazaadenosine and of 2',3',5'-tri-O-acetyl-2-amino-N(6)-cyclopentyl-1-deazaadenosine, which are very versatile intermediates for the preparation of 2-substituted 1-deazaadenosine derivatives. The two synthesized compounds showed to be quite unstable, with the N(6)-substituted derivatives being less stable than the N(6)-unsubstituted counterpart, according to the calculated HOMO-LUMO energy gap. Stability studies were performed through HPLC-MS analysis.

Synthesis and DNA topoisomerase-II inhibitory activity of unnatural nucleosides.

The synthesis and biological activities of a number of unnatural nucleosides (23-43) is described. Nucleosides have been synthesized by SnCl4-catalyzed condensation of amino sugar acetates and silylated modified pyrimidines. Few of the 2'-O-acetyl derivatives of the nucleosides were hydrolyzed to the respective hydroxy derivatives by treatment with methanol saturated with ammonia.

A versatile synthesis of dihydropyrimidinone C-nucleosides.

A versatile synthesis of N-substituted dihydropyrimidinone C-nucleosides (20-29) is described. Glycosyl amino esters (3-9), obtained by reductive alkylation of glycosyl amino esters 1 and 2, on condensation with different isocyanates afforded respective ureido derivatives (10-19) in good to quantitative yields. The latter on cyclative amidation with a combination of DBU/TBAB (tetrabutylammonium bromide)/4A molecular sieve gave the corresponding nucleosides (20-29) in good yields.