DSPL is a poised fragment library to allow rapid, cheap follow-up synthesis to provide quick SAR data. "Poised" fragments contain at least one functional group which can be synthesised using a robust, well-characterised reaction. Reactions include amide couplings, Suzuki-type aryl-aryl couplings and reductive aminations. The library was designed by analysing all of commercially available fragment space for poised-ness and selecting a chemically diverse subset.
For one challenging target, the second bromodomain of PHIP, the first ever reported hits were obtained by XChem screening; two hits were poised and were followed up accordingly, yielding compounds with improved potency in the sub-100uM range and showing good ligand efficiency - and of course detailed structural data.
More detail on the design and utility of the library can be found in our recent publication:
O. B. Cox, K. Krojer, P. Collins, O. Monteiro, R. Talon, A. Bradley, O. Fedorov, J. Amin, B. D. Marsden, J. Spencer, F. von Delft, P. E. Brennan, A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain. Chem. Sci.,2016. 7: p. 2322-2330
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