Author/Authors :
George A. Doherty، نويسنده , , Ginger X. Yang، نويسنده , , Edite Borges، نويسنده , , Linda L. Chang، نويسنده , , Malcolm MacCoss، نويسنده , , Sharon Tong، نويسنده , , Usha Kidambi، نويسنده , , Linda A. Egger، نويسنده , , Ermenegilda McCauley، نويسنده , , Gail Van Riper، نويسنده , , Richard A. Mumford، نويسنده , , John A. Schmidt، نويسنده , , William K. Hagmann، نويسنده ,
Abstract :
A series of substituted tetrahydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the α carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus α4β7 while amide substitution increased the potency of the series without increasing the specificity. Substitution of the β carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus α4β7 but with a significant loss in binding affinity for VLA-4.
