N-Isonicotinoyl-(L)-4-aminophenylalanine derivatives as tight binding VLA-4 antagonists

Abstract A series of isonicotinoyl-( l )-aminophenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. These compounds exhibit subnanomolar binding affinity to VLA-4 and significant off-rates. The interplay between off-rate, protein binding and pharmacokinetics is discussed.