Diamine containing VLA-4 antagonists Original Research Article

Design and synthesis of a library as potential VLA-4 antagonists has been accomplished, based around a proposed pharmacophoric model. Compounds possessing submicromolar potency were identified and structure–activity relationships were seen across the library. Further derivatisation produced compounds with IC50ʹs <10 nmol for inhibiting the VLA-4 mediated binding of fibronectin to RAMOS cells, providing an ideal starting point for a lead optimisation Programme.