CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors.
Alexander RP, Warrellow GJ, Eaton MA, Boyd EC, Head JC, Porter JR, Brown JA, Reuberson JT, Hutchinson B, Turner P, Boyce B, Barnes D, Mason B, Cannell A, Taylor RJ, Zomaya A, Millican A, Leonard J, Morphy R, Wales M, Perry M, Allen RA, Gozzard N, Hughes B, Higgs G.
The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig.