Identification and optimisation of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

@article{Price2007IdentificationAO,
  title={Identification and optimisation of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.},
  author={Steve W Price and Walter Bordogna and Richard James Bull and David E Clark and Peter H Crackett and Hazel Joan Dyke and Matthew I A Gill and Neil Victor Harris and Julia J. Gorski and Julia N. Lloyd and P. Lockey and Julia Mullett and Alan Geoffrey Roach and Fabien Jean Ghislain Roussel and Anne Barton White},
  journal={Bioorganic & medicinal chemistry letters},
  year={2007},
  volume={17 2},
  pages={
          370-5
        }
}
Optimisation of ADS100380, a sub-micromolar HDAC inhibitor identified using a virtual screening approach, led to a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids (6a-i), that possessed significant HDAC inhibitory activity. Subsequent functionalisation of the pendent phenyl group of compounds 6f and 6g provided analogues 6j-w with further enhanced enzyme and anti-proliferative activity. Compound 6j demonstrated efficacy in a mouse xenograft experiment. 

Similar Papers

Loading similar papers…