2-Aryladenine Derivatives as a Potent Scaffold for Adenosine Receptor Antagonists: The 6-Morpholino Derivatives.

A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A, A, A, and A adenosine receptor subtypes. Eleven purines showed potent antagonism at A, A, dual A/A, A/A, or A/A adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor.

2-Aryladenine derivatives as a potent scaffold for A, A and dual A/A adenosine receptor antagonists: Synthesis and structure-activity relationships.

From a collection containing more than 1500 academic compounds, in silico screening identified a hit for the human A adenosine receptor containing a new purine scaffold. To study the structure activity relationships of this new chemical series for adenosine receptors, a library of 24 purines was synthesized and tested in radioligand binding assays at human A, A, A and A adenosine receptor subtypes. Fourteen molecules showed potent antagonism at A, A or dual A/A adenosine receptors.

Phenolic Imidazole Derivatives with Dual Antioxidant/Antifungal Activity: Synthesis and Structure-Activity Relationship.

Background: Previous publications show that the addition of a phenolic antioxidant to an antifungal agent, considerably enhances the antifungal activity.

Objective: Synthesis of novel compounds combining phenolic units with linear or cyclic nitrogencontaining organic molecules with antioxidant/antifungal activity using methodologies previously developed in the group.

Methods: Several N- [1,2-dicyano-2- (arylidenamino) vinyl]-O-alkylformamidoximes 3 were synthesized and cyclized to 4,5-dicyano-N- (N´-alcoxyformimidoyl)-2-arylimidazoles 4 upon reflux in DMF, in the presence of manganese dioxide or to 6-cyano-8-arylpurines 5 when the reagent was refluxed in acetonitrile with an excess of triethylamine.

New Nitrogen Compounds Coupled to Phenolic Units with Antioxidant and Antifungal Activities: Synthesis and Structure⁻Activity Relationship.

A selection of 1-amino-2-arylidenamine-1,2-(dicyano)ethenes was synthesized and cyclized to 2-aryl-4,5-dicyano-1-imidazoles upon reflux in ethyl acetate/acetonitrile, in the presence of manganese dioxide. These compounds were tested for their antioxidant capacity by cyclic voltammetry, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and deoxyribose degradation assays. The minimum inhibitory concentration of all compounds was evaluated against two yeast species, and .

New chromene scaffolds for adenosine A(2A) receptors: synthesis, pharmacology and structure-activity relationships.

In silico screening of a collection of 1584 academic compounds identified a small molecule hit for the human adenosine A(2A) receptor (pK(i) = 6.2) containing a novel chromene scaffold (3a). To explore the structure-activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H-chromene-3-carboxamide derivatives was synthesized and tested in radioligand binding assays at human adenosine A(1), A(2A), A(2B) and A(3) receptors.

Synthesis of novel chromene scaffolds for adenosine receptors.

A one-pot procedure was developed for the synthesis of novel 3-[amino(methoxy)methylene]-2-oxo-3,4-dihydro-2H-chromen-4-yl)-3-cyanoacetamides and chromeno[3,4-c]pyridine-1-carbonitriles from the reaction of 2-oxo-2H-chromene-3-carbonitriles and cyanoacetamides. These chromene derivatives were identified as new scaffolds for adenosine receptors and the hits 3a, 3c, 5a, and 5b were found.

Synthesis, 3D-QSAR, and structural modeling of benzolactam derivatives with binding affinity for the D(2) and D(3) receptors.

A series of 37 benzolactam derivatives were synthesized, and their respective affinities for the dopamine D(2) and D(3) receptors evaluated. The relationships between structures and binding affinities were investigated using both ligand-based (3D-QSAR) and receptor-based methods. The results revealed the importance of diverse structural features in explaining the differences in the observed affinities, such as the location of the benzolactam carbonyl oxygen, or the overall length of the compounds.

In silico directed chemical probing of the adenosine receptor family.

One of the grand challenges in chemical biology is identifying a small-molecule modulator for each individual function of all human proteins. Instead of targeting one protein at a time, an efficient approach to address this challenge is to target entire protein families by taking advantage of the relatively high levels of chemical promiscuity observed within certain boundaries of sequence phylogeny. We recently developed a computational approach to identifying the potential protein targets of compounds based on their similarity to known bioactive molecules for almost 700 targets.

Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands.

A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D(1), D(2), and D(3) receptors. Some of these compounds showed high D(2) and/or D(3) affinity and selectivity over the D(1) receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D(2) and D(3) affinities.

Synthesis, binding affinity, and molecular docking analysis of new benzofuranone derivatives as potential antipsychotics.

The complex etiology of schizophrenia has prompted researchers to develop clozapine-related multitarget strategies to combat its symptoms. Here we describe a series of new 6-aminomethylbenzofuranones in an effort to find new chemical structures with balanced affinities for 5-HT2 and dopamine receptors. Through biological and computational studies of 5-HT2A and D2 receptors, we identified the receptor serine residues S3.

The condensation of salicylaldehydes and malononitrile revisited: synthesis of new dimeric chromene derivatives.

The reaction of salicylic aldehydes with malononitrile was reinvestigated, and the reaction pathway was followed by 1H NMR spectroscopy. A delicate control of the experimental conditions allowed the synthesis of 2-imino-2H-chromene-3-carbonitriles 1, (2-amino-3-cyano-4H-chromen-4-yl)malononitriles 2, 4-amino-5-imino-2,7-dimethoxy-5H-chromeno[3,4-c]pyridine-1-carbonitrile 12, and (4,5-diamino-1-cyano-1,10b-dihydro-2H-chromeno[3,4-c]pyridin-2-ylidene)malononitrile 13. Two novel 2-iminochromene dimers, with structures 8 and 9, were isolated and fully characterized.

Synthesis and binding affinity of new pyrazole and isoxazole derivatives as potential atypical antipsychotics.

We describe the synthesis and binding affinities on D(2), 5-HT(2A) and 5-HT(2C) receptors of 6-aminomethyl-6,7-dihydro-1H-indazol-4(5H)-ones and 6-aminomethyl-6,7-dihydro-3-methyl-benzo[d]isoxazol-4(5H)-ones, as conformationally constrained butyrophenone analogues. One of the new compounds showed good in vitro binding features, and a Meltzer's ratio characteristic of an atypical antipsychotic profile.

Oxidative stress protection by newly synthesized nitrogen compounds with pharmacological potential.

In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals' buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds.