Go with the flow: de-orphaning focused combinatorial libraries
© Reutlinger et al; licensee Chemistry Central Ltd. 2014
Published: 11 March 2014
The fast pace of drug discovery programs, aided by high-throughput screening campaigns, often relies on the generation of combinatorial libraries to identify new chemical entities. The Ugi 4- and 3-component reactions in particular , have proven to be robust in producing both tool compounds and drugs [2, 3]. Here we report a high-throughput entry into the imidazopyridine scaffold, using a microfluidic-assisted synthesis setup, coupled to a target prediction tool to de-orphan a focused compound library with high success rate, and identify an innovative GPCR-inhibiting chemotype. Combinatorial compounds were correctly identified as ligand-efficient adenosine A1/2B, and adrenergic α1A/B inhibitors with K i values in the low micromolar range.
- Ugi M: Angew Chem Int Ed. 1962, 1: 8-21. 10.1002/anie.196200081.View ArticleGoogle Scholar
- Beck M, Srivastava S, Khoury K, Herdtweck E, Dömling A: Mol Div. 2010, 14: 479-491. 10.1007/s11030-010-9249-2.View ArticleGoogle Scholar
- Kalinski C, Lemoine H, Schmidt J, Burdack C, Kolb J, Umkehrer M, Ross G: Synthesis. 2008, 24: 4007-4011.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.