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Combining On‐Chip Synthesis of a Focused Combinatorial Library with Computational Target Prediction Reveals Imidazopyridine GPCR Ligands
Author(s) -
Reutlinger Michael,
Rodrigues Tiago,
Schneider Petra,
Schneider Gisbert
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201307786
Subject(s) - combinatorial synthesis , imidazopyridine , combinatorial chemistry , computer science , computational biology , ligand (biochemistry) , prioritization , g protein coupled receptor , microfluidics , drug discovery , chemistry , nanotechnology , biology , engineering , receptor , materials science , biochemistry , management science
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.