Structure-Based Screening of Uncharted Chemical Space for Atypical Adenosine Receptor Agonists.

ABSTRACT: Small molecule screening libraries cover only a small fraction of the astronomical number of possible drug-like compounds, limiting the success of ligand discovery efforts. Computational screening of virtual libraries representing unexplored chemical space could potentially bridge this gap. Drug development for adenosine receptors (ARs) as targets for inflammation and cardiovascular diseases has been hampered by the paucity of agonist scaffolds. To identify novel AR agonists, a virtual library of synthetically tractable nucleosides with alternative bases was generated and structure-based virtual screening guided selection of compounds for synthesis. Pharmacological assays were carried out at three AR subtypes for 13 ribosides. Nine compounds displayed significant activity at the ARs, and s

SUBMITTER: Rodriguez D 

PROVIDER: S-EPMC5207038 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature