Author/Authors :
Georgette M. Castanedo، نويسنده , , Fredrick C. Sailes، نويسنده , , Nathan J. P. Dubree، نويسنده , , John B. Nicholas، نويسنده , , Lisa Caris، نويسنده , , Kevin Clark، نويسنده , , Susan M. Keating، نويسنده , , Maureen H. Beresini، نويسنده , , W.Henry Chiu، نويسنده , , Sherman Fong، نويسنده , , James C. Marsters Jr، نويسنده , , David Y. Jackson، نويسنده , , Daniel P. Sutherlin، نويسنده ,
Abstract :
Two structural classes of dual α4β1/α4β7 integrin antagonists were investigated via solid-phase parallel synthesis. Using an acylated amino acid backbone, lead compounds containing biphenylalanine or tyrosine carbamate scaffolds were optimized for inhibition of α4β1/VCAM and α4β7/MAdCAM. A comparison of the structure–activity relationships in the inhibition of the α4β7/MAdCAM interaction for substituted amines employed in both scaffolds suggests a similar binding mode for the compounds.
