Author/Authors :
Jun Chiba، نويسنده , , Nobuo Machinaga، نويسنده , , Tohru Takashi، نويسنده , , Akio Ejima، نويسنده , , Gensuke Takayama، نويسنده , , Mika Yokoyama، نويسنده , , Atsushi Nakayama، نويسنده , , John J. Baldwin، نويسنده , , B. Edward McDonald and William L. Siegmann، نويسنده , , Kurt W. Saionz، نويسنده , , Robert Swanson، نويسنده , , Zahid Hussain، نويسنده , , Angela Wong، نويسنده ,
Abstract :
An investigation into the structure–activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative (13d: IC50 = 4.4 nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration.
