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  • Poster presentation
  • Open Access

Go with the flow: de-orphaning focused combinatorial libraries

  • 1,
  • 1,
  • 1 and
  • 1
Journal of Cheminformatics20146 (Suppl 1) :P49

https://doi.org/10.1186/1758-2946-6-S1-P49

  • Published:

Keywords

  • Combinatorial Library
  • High Success Rate
  • Target Prediction
  • Fast Pace
  • Micromolar Range

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 [1], 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.

Authors’ Affiliations

(1)
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zurich, 8093, Switzerland

References

  1. Ugi M: Angew Chem Int Ed. 1962, 1: 8-21. 10.1002/anie.196200081.View ArticleGoogle Scholar
  2. 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
  3. Kalinski C, Lemoine H, Schmidt J, Burdack C, Kolb J, Umkehrer M, Ross G: Synthesis. 2008, 24: 4007-4011.View ArticleGoogle Scholar

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