Author/Authors :
Allen J. Duplantier، نويسنده , , Gretchen E. Beckius، نويسنده , , Robert J. Chambers، نويسنده , , Louis S. Chupak، نويسنده , , Teresa H. Jenkinson، نويسنده , , Anne S. Klein، نويسنده , , Kenneth G. Kraus، نويسنده , , Elizabeth M. Kudlacz، نويسنده , , Michael W. McKechney، نويسنده , , Martin Pettersson، نويسنده , , Carrie A. Whitney، نويسنده , , Anthony J. Milici، نويسنده ,
Abstract :
A series of isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives derived from LDV was found to be a potent antagonist of the α4β1 integrin. The synthesis and SAR leading up to 3-[3-(1-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-3-methyl-butyl)-isoxazol-5-yl]-propionic acid (22) are reported. In an allergic mouse model, compound 22 was efficacious delivered systemically (58% inhib @ 10 mg/kg, sc) as well as by intra-tracheal instillation (ED50=2 μg/kg).
