1,2,4-Triazolo[1,5-a]quinoxaline as a Versatile Tool for the Design of Selective Human A3 Adenosine Receptor Antagonists: Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives

doi:10.1021/JM0504149

Paper

1,2,4-Triazolo[1,5-a]quinoxaline as a Versatile Tool for the Design of Selective Human A3 Adenosine Receptor Antagonists: Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives

Published Nov 11, 2005 · D. Catarzi, V. Colotta, F. Varano

Journal of Medicinal Chemistry

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Abstract

A number of 4-oxo-substituted 1,2,4-triazolo[1,5-a]quinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1−15) but also a carboxylate group (16−28, 32−36) or a hydrogen atom (29−31) were designed as human A3 (hA3) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4-methoxyphenyl)-1,2,4-triazolo[1,5-a]quinoxalin-4-one (8), which can be considered one of the most potent and selective hA3 adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16−28 and 32−36) maintained good hA3 AR binding activity but, most importantly and interestingly, produced a large increase in hA3 versus hA1 selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA3 receptor recognition site, thus hi...

In Vitro Study

Study Snapshot

1,2,4-triazolo[1,5-a]quinoxaline is a versatile tool for designing selective human A3 adenosine receptor antagonists, with 2-(4-methoxyphenyl)-1,2,4-triazolo[1,5-a]quinoxalin

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

1,2,4-Triazolo[1,5-a]quinoxaline as a Versatile Tool for the Design of Selective Human A3 Adenosine Receptor Antagonists: Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives

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References

Citations

Divergent Synthesis of Trifluoromethyl-Substituted 1,2-Dihydroquinoxalines and Diimines by Cascade Reactions of CF3-Imidoyl Sulfoxonium Ylides with Azo Compounds.

A base-mediated cascade reaction of CF3-imidoyl sulfoxonium ylides and azo compounds allows for facile access to trifluoromethyl-substituted 1,2-dihydroquinoxalines and diimines in moderate to excellent yields.

Chemoenzymatic Asymmetric Synthesis of Complex Heterocycles: Dihydrobenzoxazinones and Dihydroquinoxalinones

Chemoenzymatic synthesis routes enable facile preparation of optically pure dihydrobenzoxazinones and dihydroquinoxalinones, offering attractive alternatives for pharmaceuticals and agrochemicals.

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

Catalytic asymmetric aza-Diels-Alder reaction (CASADAR) has proven effective for enantioselective synthesis of useful chiral nitrogen-containing heterocycles, with potential applications in pharmacology.

Carbene-Catalyzed α-Carbon Amination of Chloroaldehydes for Enantioselective Access to Dihydroquinoxaline Derivatives.

This NHC-catalyzed -carbon amination of chloroaldehydes provides enantioselective access to optically enriched dihydroquinoxaline derivatives, which are core structures in natural products and synthetic bioactive molecules.

Iron- or Zinc-Mediated Synthetic Approach to Enantiopure Dihydroquinoxalinones

This study developed a general and efficient method for synthesizing enantiopure dihydroquinoxalinones using naturally occurring amino acids, yielding moderate to high yields and 7 new compounds.

A3 Adenosine Receptors as Modulators of Inflammation: From Medicinal Chemistry to Therapy

Targeting the A3 adenosine receptor subtype offers promising therapeutic options for inflammatory diseases, cancer, and other conditions, with potential for personalized medicine approaches.

Development of novel pyridazinone-based adenosine receptor ligands.

Compound 5 (5-ethyl-7-(thiazol-2-yl)thieno[2,3-d ]pyridazin-4(5H)-one) shows promising potential as a new adenosine receptor ligand due to its simple synthetic process and easy decoration.