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Your search keyword '"Tricyclic heteroaromatic systems"' showing total 3 results
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3 results on '"Tricyclic heteroaromatic systems"'

1. 1,2,4-Triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A3 receptor antagonists. Synthesis, structure–affinity relationships and molecular modeling studies

Author

Daniela Catarzi, Flavia Varano, Daniela Poli, Lucia Squarcialupi, Marco Betti, Letizia Trincavelli, Claudia Martini, Diego Dal Ben, Ajiroghene Thomas, Rosaria Volpini, and Vittoria Colotta

Subjects
G protein-coupled receptors, Organic Chemistry, Clinical Biochemistry, Drug Discovery, Tricyclic heteroaromatic systems, Pharmaceutical Science, Molecular Medicine, Adenosine receptor antagonists, Triazoloquinoxalines, Ligand-receptor modeling studies, Molecular Biology, Biochemistry
Published
2015

2. Pyrazolo[1,5-c]quinazoline derivatives and their simplified analogues as adenosine receptor antagonists: Synthesis, structure–affinity relationships and molecular modeling studies

Author

Catia Lambertucci, Flavia Varano, Gloria Cristalli, Lucia Squarcialupi, Guido Filacchioni, Daniela Catarzi, Fabrizio Vincenzi, Vittoria Colotta, Pier Andrea Borea, Daniela Poli, Diego Dal Ben, and Katia Varani

Subjects
Molecular model, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Adenosine receptor antagonists, CHO Cells, Molecular Dynamics Simulation, Biochemistry, NO, Structure-Activity Relationship, chemistry.chemical_compound, Quinoxaline, G protein-coupled receptors, Cricetinae, Drug Discovery, medicine, Animals, Humans, Receptor, Molecular Biology, G protein-coupled receptor, chemistry.chemical_classification, Receptor, Adenosine A3, Organic Chemistry, Pyrazoloquinazolines, G protein-coupled receptors, Adenosine receptor antagonists, Pyrazoloquinazolines, Tricyclic heteroaromatic systems, Ligand–receptor modeling studies, Adenosine receptor, Adenosine, Purinergic P1 Receptor Antagonists, chemistry, Quinazolines, Pyrazoles, Tricyclic heteroaromatic systems, Molecular Medicine, Selectivity, Ligand–receptor modeling studies, Tricyclic, medicine.drug
Abstract

The 1,2,4-triazolo[1,5-a]quinoxaline (TQX) scaffold was extensively investigated in our previously reported studies and recently, our attention was focused at position 5 of the tricyclic nucleus where different acyl and carboxylate moieties were introduced (compounds 2–15). This study produced some interesting compounds endowed with good hA3 receptor affinity and selectivity. In addition, to find new insights about the structural requirements for hA3 receptor–ligand interaction, the tricyclic TQX ring was destroyed yielding some 1,2,4-triazole derivatives (compounds 16–23). These simplified compounds, though maintaining the crucial structural requirements for adenosine receptor–ligand interaction, have a very low hA3 adenosine receptor affinity, the only exception being compound 23 (1-[3-(4-methoxyphenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]-3-phenylurea) endowed with a Ki value in the micro-molar range and high hA3 selectivity versus both hA1 and hA2A AR subtypes. Evaluation of the side products obtained in the herein reported synthetic pathways led to the identification of some new triazolo[1,5-a]quinoxalines as hA3AR antagonists (compounds 24–27). These derivatives, though lacking the classical structural requirements for the anchoring at the hA3 receptor site, show high hA3 affinity and in some case selectivity versus hA1 and hA2A subtypes. Molecular docking of the herein reported tricyclic and simplified derivatives was carried out to depict their hypothetical binding mode to our model of hA3 receptor.

Published
2013

3. Synthesis, structure–affinity relationships, and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists

Author

Vittoria Colotta, Pier Andrea Borea, Flavia Varano, Diego Dal Ben, Fabrizio Vincenzi, Lucia Squarcialupi, Ombretta Lenzi, Guido Filacchioni, Gloria Cristalli, Catia Lambertucci, Katia Varani, and Daniela Catarzi

Subjects
Models, Molecular, Steric effects, Molecular model, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Adenosine receptor antagonists, CHO Cells, Ligand-receptor modeling studies, Pyrazoloquinolines, Crystallography, X-Ray, Biochemistry, Chemical synthesis, Structure-Activity Relationship, chemistry.chemical_compound, Cricetulus, G protein-coupled receptors, Cricetinae, Drug Discovery, Animals, Humans, Computer Simulation, Molecular Biology, Organic Chemistry, Quinoline, Ligand (biochemistry), Adenosine receptor, Affinities, Purinergic P1 Receptor Antagonists, chemistry, Lipophilicity, Quinolines, Tricyclic heteroaromatic systems, Pyrazoles, Molecular Medicine
Abstract

This paper reports the study of new 2-phenyl- and 2-methylpyrazolo[3,4-c]quinolin-4-ones (series A) and 4-amines (series B), designed as adenosine receptor (AR) antagonists. The synthesized compounds bear at the 6-position various groups, with different lipophilicity and steric hindrance, that were thought to increase human A(1) and A(2A) AR affinities and selectivities, with respect to those of the parent 6-unsubstituted compounds. In series A, this modification was not tolerated since it reduced AR affinity, while in series B it shifted the binding towards the hA(1) subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A(2A)AR-based homology models of the A(1) and A(3) ARs and at the A(2A)AR crystal structure were carried out.

Published
2011

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