New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies.

doi:10.1021/JM070123V

Paper

New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies.

Published Aug 1, 2007 · V. Colotta, D. Catarzi, F. Varano

Journal of medicinal chemistry

Q1 SJR score

51

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

This paper reports the study of some 2-arylpyrazolo[3,4-c]quinolin-4-ones, 4-amines, and 4-amino-substituted derivatives designed as human A3 adenosine receptor (AR) antagonists. Most of the herein reported compounds showed a nanomolar affinity toward the hA3 receptor subtype and different degrees of selectivity that resulted to be strictly dependent on the presence and nature of the substituent on the 4-amino group. Bulky and lipophilic acyl groups, as well as the benzylcarbamoyl residue, afforded highly potent and selective hA3 receptor antagonists. The selected 4-diphenylacetylamino-2-phenylpyrazoloquinoline (25) and 4-dibenzoylamino-2-(4-methoxyphenyl)pyrazoloquinoline (36), tested in an in vitro rat model of cerebral ischemia, prevented the irreversible failure of synaptic activity induced by oxygen and glucose deprivation in the hippocampus. The observed structure-affinity relationships of this class of antagonists were also exhaustively rationalized using the recently published ligand-based homology modeling (LBHM) approach.

In Vitro Study

Study Snapshot

New 2-arylpyrazolo[3,4-c]quinoline derivatives show potent and selective human A3 adenosine receptor antagonists, potentially preventing synaptic failure in cerebral ischemia.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies.

Sign up to use Study Snapshot

References

Citations

Predicción de la afinidad de ligandos antagonistas por receptores de adenosina A2A usando árboles de decisión

This study developed a methodology to predict ligand-RAA2A affinity using decision tree algorithms and descriptors from 0D to 2D, achieving accuracy, specificity, and selectivity greater than 90%.

Structural simplification: an efficient strategy in lead optimization

Structural simplification in lead optimization improves efficiency and success rates in drug discovery and development by avoiding "molecular obesity" and enhancing synthetic accessibility, pharmacokinetic profiles, and reducing side effects.

Ring-Opening of Indoles: An Unconventional Route for the Transformation of Indoles to 1 H-Pyrazoles Using Lewis Acid.

This study developed an unconventional ring-opening strategy for transforming indoles to pyrazoles, providing a wide scope of differently substituted pyrazoles under transition-metal and ligand-free conditions.

Synthesis and mesomorphism behaviour of chalcones and pyrazoles type compounds as photo-luminescent materials

Pyrazole derivatives are the only liquid crystal materials among the synthesized compounds, all of which exhibit photo-luminescent properties in crystalline solid state and mesophase.

Chemoinformatics Profiling of the Chromone Nucleus as a MAO-B/A2AAR Dual Binding Scaffold

The chromone nucleus shows potential as a MAO-B/A2AAR dual binding scaffold, offering potential for Parkinson's disease disease-modifying therapies.

Structure and spectroscopic investigations of a bi-dentate N′-[(4-ethylphenyl)methylidene]-4-hydroxybenzohydrazide and its Co(II), Ni(II), Cu(II) and Cd(II) complexes: Insights relevant to biological properties

The novel ligand N′-[(4-ethylphenyl)methylidene]-4-hydroxy benzohydrazide (HL) and its complexes show DNA cleavage activity and in vitro antibacterial activity against Gram-positive and Gram-negative bacteria.

Imidazo[1,2-a]pyrazin-8-amine core for the design of new adenosine receptor antagonists: Structural exploration to target the A3 and A2A subtypes.

The imidazo[1,2-a]pyrazine ring system is a promising core skeleton for designing novel adenosine receptor antagonists targeting either the A3 or A2A subtypes, with potential therapeutic applications in treating cerebral ischemia.

Synthesis, Enzyme Inhibition, and Molecular Docking Studies of Hydrazones from Dichlorophenylacetic Acids

Hydrazones 5a-i show potent -glucosidase inhibitory potential, with molecular docking studies revealing their binding mode in the active sites of -glucosidase and urease enzymes.