New insight into adenosine receptors selectivity derived from a novel series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamides and furamides

作者：Inamdar Gajanan S; Pandya Amit N; Thakar Hardik M; Sudarsanam Vasudevan; Kachler Sonja; Sabbadin Davide; Moro Stefano; Klotz Karl Norbert; Vasu Kamala K^*

来源：European Journal of Medicinal Chemistry, 2013, 63: 924-934.

DOI：10.1016/j.ejmech.2013.03.020

• 2-Aminothiazole
• Adenosine receptors
• Selectivity profile
• Structure activity relationship
• Receptor models
• Molecular docking
• Membrane molecular dynamics

A series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamide and furamide analogues were investigated in radioligand binding studies at adenosine receptor subtypes with an aim to obtain potent and selective adenosine receptor ligands. Benzamide and furamide linked to thiazole was found to be crucial for high adenosine receptor affinity. The most potent compound indentified in this study was 5d with low nanomolar affinity for all four adenosine receptor subtypes. Compounds 5a and 5g showed moderate selectivity for A(2A) adenosine receptors. Molecular docking versus all four human adenosine receptors combined with membrane molecular dynamics studies were performed to rationalise the peculiar selectivity profile of 5d antagonist.

• 出版日期2013-5