A1 adenosine receptor antagonists have been proposed to possess an interesting range of potential therapeutic applications. The authors have already reported the synthesis and the biol. characterization of a family of pyrazolo[3,4-b]pyridine derivs. as A1 adenosine ligands endowed with an antagonistic profile. In the present work, the authors report the LC sepn. of enantiomers of the authors' most active A1 antagonists together with the detn. of their abs. configuration by x-ray crystal structure anal. Biol. assays confirmed a different activity for the two enantiomers, with the R one showing the higher human A1AR affinity. The authors also developed a homol. model of this receptor subtype to suggest a binding disposition of the ligands into the hA1AR. All of the obtained data suggest that the compd.'s chirality plays a key role in A1 affinity.

Substituted pyrazolo[3,4-b]pyridines as human A(1) adenosine antagonists: Developments in understanding the receptor stereoselectivity

BRULLO, CHIARA;MUSUMECI, FRANCESCA;SCHENONE, SILVIA;
2011-01-01

Abstract

A1 adenosine receptor antagonists have been proposed to possess an interesting range of potential therapeutic applications. The authors have already reported the synthesis and the biol. characterization of a family of pyrazolo[3,4-b]pyridine derivs. as A1 adenosine ligands endowed with an antagonistic profile. In the present work, the authors report the LC sepn. of enantiomers of the authors' most active A1 antagonists together with the detn. of their abs. configuration by x-ray crystal structure anal. Biol. assays confirmed a different activity for the two enantiomers, with the R one showing the higher human A1AR affinity. The authors also developed a homol. model of this receptor subtype to suggest a binding disposition of the ligands into the hA1AR. All of the obtained data suggest that the compd.'s chirality plays a key role in A1 affinity.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/293993
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