Products Cited in Publications Worldwide Design, synthesis and evaluation of amino-3, 5-dicyanopyryridines and thieno [2, 3-b] pyridines as ligands of adenosine receptors

Design, synthesis and evaluation of amino-3, 5-dicyanopyryridines and thieno [2, 3-b] pyridines as ligands of adenosine receptors

Nkomba, Gaofenngwe; Terre'Blanche, Gisella; van Rensburg, Helena Dorathea Janse; Legoabe, Lesetja J

DOI: PMID:

Abstract

Due to the implication of adenosine in seizure suppression, adenosine-based therapies such as adenosine receptor (AR) agonists have been investigated. This study aimed at investigating thieno[2,3 b]pyridine derivatives as non-nucleoside A1 agonists that could be used in pharmaco-resistant epilepsy (PRE). Compound 7c (thieno[2,3-b]pyridine derivative), displayed good binding a nity to the rA1 AR (Ki = 61.9 nM). This could be a breakthrough for further investigation of this heterocyclic scaffold as potential ligand. In silico evaluation of this compound raised bioavailability concerns but performed well on drug likeness tests. The effect of intramolecular cyclisation that occurs during synthesis of thieno[2,3 b]pyridines from the lead compounds, amino-3,5-dicyanopyridine derivatives ( 6a-s) in relation to AR binding was also evaluated. A signi cant loss of activity against rA1/rA2A ARs with cyclisation was revealed. Amino-3,5-dicyanopyridines exhibited greater a nity towards rA1 ARs (Ki

Keywords

Amino-3,5-dicyanopyryridines ; Thieno[2,3-b]pyridines ; Intramolecular cyclisation ; Adenosine A1/A2A receptors ; Epilepsy

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