Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H₁ antagonists. Part I.
Furber M, Alcaraz L, Luckhurst C, Bahl A, Beaton H, Bowers K, Collington J, Denton R, Donald D, Kinchin E, MacDonald C, Rigby A, Riley R, Soars M, Springthorpe B, Webborn P.
The discovery of potent small molecule dual antagonists of the human CCR3 and H(1) receptors is described for the treatment of allergic diseases, for example, asthma and allergic rhinitis. Optimizing in vitro potency and metabolic stability, starting from a CCR1 lead compound, led to compound 20 with potent dual CCR3/H(1) activity and in vitro metabolic stability.