The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains

Duncan Hay; Oleg Fedorov; Panagis Filippakopoulos; Sarah Martin; Martin Philpott; Sarah Picaud; David S. Hewings; Sagar Uttakar; Tom D. Heightman; Stuart J. Conway; Stefan Knapp; Paul E. Brennan

doi:10.1039/C2MD20189E

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains†‡

Duncan Hay,^a Oleg Fedorov,^a Panagis Filippakopoulos,^a Sarah Martin,^a Martin Philpott,^a Sarah Picaud,^a David S. Hewings,^b Sagar Uttakar,^a Tom D. Heightman,§^a Stuart J. Conway,^b Stefan Knapp^a and Paul E. Brennan*^a

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^a Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK
E-mail: paul.brennan@sgc.ox.ac.uk

^b Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK

Abstract

Simple 1-substituted 5- and 6-isoxazolyl-benzimidazoles have been shown to be potent inhibitors of the BET bromodomains with selectivity over the related bromodomain of CBP. The reported inhibitors were prepared from simple starting materials in two steps followed by separation of the regioisomers or regioselectively in three steps.

MedChemComm

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains†‡

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The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains

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