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Synthesis and 3D QSAR of new pyrazolo[3,4-b]pyridines: potent and selective inhibitors of A1 adenosine receptors.

Authors :
Manetti F
Schenone S
Bondavalli F
Brullo C
Bruno O
Ranise A
Mosti L
Menozzi G
Fossa P
Trincavelli ML
Martini C
Martinelli A
Tintori C
Botta M
Source :
Journal of medicinal chemistry [J Med Chem] 2005 Nov 17; Vol. 48 (23), pp. 7172-85.
Publication Year :
2005

Abstract

A number of 4-aminopyrazolo[3,4-b]pyridines 5-carboxylic acid esters (2-8) were synthesized and evaluated for their binding affinity at the A1, A2A, and A3 adenosine receptors (AR), in bovine cortical membranes, as well as for their affinity toward human A1AR (hA1AR). Some of the new compounds were characterized by a high affinity and selectivity toward the A1 receptor subtype, showing a significant improvement in comparison with other pyrazolo-pyridines previously reported in the literature. In particular the methyl ester 2h as well as the isopropyl ester 5h, both of them bearing a p-methoxyphenylethylamino side chain at the position 4, presented Ki values of 6 and 7 nM, respectively. To rationalize the relationships between structure and affinity of the novel compounds, a 3D QSAR model was also generated starting from compounds belonging to different classes of known A1AR antagonists.

Details

Language :
English
ISSN :
0022-2623
Volume :
48
Issue :
23
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
16279775
Full Text :
https://doi.org/10.1021/jm050407k