Synthesis and Structure‐Activity Relationships of 4‐Cycloalkylamino‐1, 2, 4‐triazolo[4, 3‐a]quinoxalin‐1‐ one Derivatives as A<sub>1</sub> and A<sub>3</sub> Adenosine Receptor Antagonists

Colotta, Vittoria; Catarzi, Daniela; Varano, Flavia; Filacchioni, Guido; Martini, Claudia; Trincavelli, Maria Letizia; Lucacchini, Antonio

doi:10.1002/ardp.200300816

Cited by 9 publications

(4 citation statements)

References 21 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The series of 1,2,4-triazolo[4,3-a]quinoxalin-1-ones has previously been reviewed [35]. The most effective A 1 AR ligand (34) possesses cyclopentyl as the 4-aminosubstituent and an NO 2 group at C(8) [58][59][60]. 1,2,4-Triazolo[1,5-a]quinoxalin-4-amines containing at position-2 an ethyl carboxylate group or a hydrogen atom have been studied for their binding affinity at bovine A 1 and A 2A ARs.…”

Section: Tricyclic Fused Heteroaromatic Systemsmentioning

confidence: 99%

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Yuzlenko

Kieć‐Kononowicz

2006

CMC

View full text Add to dashboard Cite

This review summarizes the current tendencies observed in the past 5 years in the development of A(1) and A(2A) adenosine receptor antagonists performed in various academia and industry. A(1) and A(2A) AR antagonists are as well xanthines as heteroaromatic derivatives and are most commonly 6:5 fused heteroatomic compounds. Among xanthine-based compounds, some common features could be pointed out. The recent A(1) AR ligands which show good biological profile, possess long alkyl chains in position 1 and 3 as well as bulky C(8)-substituent, while A(2A) AR antagonists with a high A(2A) AR affinity are C(8)-styryl substituted with N(1)-alkyl/alkynyl moiety or fused tricyclic xanthines possessing heteroatom(s) in the third cycle. The research in the field of heteroaromatic A(1) and A(2A) ARs antagonists impressively has a wide range. Ligands are as well non-fused monocyclic substituted compounds as fused bi- and tricyclic derivatives with the nitrogen, oxygen and sulfur heteroatoms. Most often, adenosine A(1) receptor non-xanthine antagonists are adenine-based, having substituted amino group and variable nitrogen atoms positions in the molecules. A(2A) AR ligands show good affinity when furanyl function, which is crucial for binding, is present in the fused bicyclic and tricyclic analogs. Moreover, tricyclic nitrogen containing antagonists in order to be active, frequently possess long-alkylphenyl moiety.

show abstract

Section: Tricyclic Fused Heteroaromatic Systemsmentioning

confidence: 99%

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Yuzlenko

Kieć‐Kononowicz

2006

CMC

View full text Add to dashboard Cite

show abstract

“…Over the past decade, we have focused a part of our research on the study of AR antagonists belonging to strictly correlated classes of tricyclic compounds. − One of these classes is represented by the 4-amino-2-aryl-1,2,4-triazolo[4,3- a ]quinoxalin-1-one derivatives, which were intensively investigated by evaluating the effect of different substituents on the 4-amino group, the 2-phenyl ring, and the fused benzo ring (Chart ). ,− These studies led to the identification of some groups that, introduced one by one in a suitable position of the 1,2,4-triazolo[4,5- a ]quinoxalin-1-one scaffold, afforded high A 3 AR affinity and good selectivity. These groups are acyl residues, such as the acetyl or benzoyl groups, on the 4-amino group (compounds A and B ), the para methoxy substituent on the 2-phenyl ring (compound C ), and the 6-nitro group (compound D ) .…”

Section: Introductionmentioning

confidence: 99%

4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

et al. 2006

Self Cite

View full text Add to dashboard Cite

A structural investigation on some 4-amido-2-phenyl-1,2-dihydro-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, designed as human A3 adenosine receptor (hA3 AR) antagonists, is described. In the new derivatives, some acyl residues with different steric bulk were introduced on the 4-amino group, and their combination with the 4-methoxy group on the 2-phenyl moiety, and/or the 6-nitro/6-amino substituent on the fused benzo ring, was also evaluated. Most of the new derivatives were potent and selective hA3 AR antagonists. SAR analysis showed that hindering and lipophilic acyl moieties not only are well tolerated but even ameliorate the hA3 affinity. Interestingly, the 4-methoxy substituent on the appended 2-phenyl moiety, as well as the 6-amino group, always exerted a positive effect, shifting the affinity toward the hA3 receptor subtype. In contrast, the 6-nitro substituent exerted a variable effect. An intensive molecular modeling investigation was performed to rationalize the experimental SAR findings.

show abstract

“…125 I]AB-MECA binding assay to transfected cell membranes was carried out as previously described [36]. In brief, the cell membranes (80 lg per assay) were incubated in 100 lL of 50 mM Tris, 10 mM MgCl 2 and 1 mM EDTA (pH 8.12) which contained […”

Section: A 2a Receptor Binding Assaymentioning

confidence: 99%

“…At removal, the cells were harvested by centrifugation at 500 g. The crude membranes were prepared as described by Olah et al [36]. […”

Section: A 2a Receptor Binding Assaymentioning

confidence: 99%

Synthesis of New 2‐Phenyladenines and 2‐Phenylpteridines and Biological Evaluation as Adenosine Receptor Ligands

Giorgi¹,

Biagi

Livi

et al. 2007

Archiv der Pharmazie

View full text Add to dashboard Cite

Synthesis and biological assays of a series of 2-phenylpteridine derivatives are described to compare their affinities to adenosine receptors with those of the corresponding adenines, purposely prepared, and 8-azaadenines previously described. This study demonstrates that the enlargement of the five-membered ring of the adenine nucleus to a six-membered one is a modification that does not allow the molecules to maintain high activity towards adenosine receptors; in fact, pteridine derivatives did not show themselves to be good adenosine receptor ligands. On the contrary, N(6)-cycloalkyl- or N(6)-alkyl-2-phenyladenines showed a very high affinity and selectivity for A(1) adenosine receptors. We demonstrate also that the 9-benzyl substituent is crucial for conferring high affinity for A(3) receptors to molecules having a 2-phenyladenine-like nucleus.

show abstract

Synthesis and Structure‐Activity Relationships of 4‐Cycloalkylamino‐1, 2, 4‐triazolo[4, 3‐a]quinoxalin‐1‐ one Derivatives as A₁ and A₃ Adenosine Receptor Antagonists

Cited by 9 publications

References 21 publications

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

Synthesis of New 2‐Phenyladenines and 2‐Phenylpteridines and Biological Evaluation as Adenosine Receptor Ligands

Contact Info

Product

Resources

About

Synthesis and Structure‐Activity Relationships of 4‐Cycloalkylamino‐1, 2, 4‐triazolo[4, 3‐a]quinoxalin‐1‐ one Derivatives as A1 and A3 Adenosine Receptor Antagonists

Cited by 9 publications

References 21 publications

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A3 Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

Synthesis of New 2‐Phenyladenines and 2‐Phenylpteridines and Biological Evaluation as Adenosine Receptor Ligands

Contact Info

Product

Resources

About

Synthesis and Structure‐Activity Relationships of 4‐Cycloalkylamino‐1, 2, 4‐triazolo[4, 3‐a]quinoxalin‐1‐ one Derivatives as A₁ and A₃ Adenosine Receptor Antagonists

4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies