Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration.

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Woodrow MD, Ballantine SP, Barker MD, Clarke BJ, Dawson J, Dean TW, Delves CJ, Evans B, Gough SL, Guntrip SB, Holman S, Holmes DS, Kranz M, Lindvaal MK, Lucas FS, Neu M, Ranshaw LE, Solanke YE, Somers DO, Ward P, Wiseman JO

Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration.

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5261-5. doi: 10.1016/j.bmcl.2009.04.012. Epub 2009 Apr 9.

PubMed ID

19656678 [ View in PubMed

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Abstract

Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-alpha from isolated human peripheral blood mononuclear cells with a pIC(50) of 11.1. GSK256066 also has a suitable profile for inhaled dosing.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(R)-Rolipram	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	IC 50 (nM)	39.81	N/A	N/A	Details