Author/Authors :
Linda L. Chang، نويسنده , , Quang Truong، نويسنده , , George A. Doss، نويسنده , , Malcolm MacCoss، نويسنده , , Kathryn Lyons، نويسنده , , Ermengilda McCauley، نويسنده , , Richard Mumford، نويسنده , , Gail Forrest، نويسنده , , Stella Vincent، نويسنده , , John A. Schmidt، نويسنده , , William K. Hagmann، نويسنده ,
Abstract :
VLA-4 is implicated in several inflammatory and autoimmune disease states. A series of cyclic β-amino acids (β-aa) was studied as VLA-4 antagonists. Binding affinity was highly dependent on the dihedral angle ( ) between the amino and the carboxyl termini of the β-aa. Compound 5m where the β-aa is embedded in a bicycle possesses the most preferred (120°). It is a potent and bioavailable VLA-4 antagonist (VCAM-Ig α4β1 IC50 = 54 nM, rat po F = 49%).
Keywords :
?4?1 , autoimmune , ?-Amino acid , Conformational restriction , Bioavailable , Bicyclic , VLA-4 antagonists , integrin , anti-inflammatory
