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

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

  • Bioorg Med Chem Lett. 2007 Jan 15;17(2):370-5. doi: 10.1016/j.bmcl.2006.10.048.
Steve Price 1,  Walter Bordogna,  Richard J Bull,  David E Clark,  Peter H Crackett,  Hazel J Dyke,  Matthew Gill,  Neil V Harris,  Julia Gorski,  Julia Lloyd,  Peter M Lockey,  Julia Mullett,  Alan G Roach,  Fabien Roussel,  Anne B White
Affiliations

Affiliation

  • 1 Argenta Discovery Ltd, 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, UK. [email protected]
PMID: 17095213 DOI: 10.1016/j.bmcl.2006.10.048
Abstract

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.

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