Combining On‐Chip Synthesis of a Focused Combinatorial Library with Computational Target Prediction Reveals Imidazopyridine GPCR Ligands1. Issue 2 (26th November 2013)

• Record Type: Journal Article
• Authors: Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 2(2014)
• Page Start: 582
• Page End: 585
• Publication Date: 2013-11-26
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201307786
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Using the example of the Ugi three‐component reaction we report a fast and efficient microfluidic‐assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand–target associations. We identified an innovative GPCR‐modulating combinatorial chemotype featuring ligand‐efficient adenosine A_1/2B and adrenergic α_1A/B receptor antagonists. Our results suggest the tight integration of microfluidics‐assisted synthesis with computer‐based target prediction as a viable approach to rapidly generate bioactivity‐focused combinatorial compound libraries with high success rates.</p> </abstract>