NEW SERINE-PROTEASE INHIBITORS WITH LEUKOTRIENE B-4 (LTB4) RECEPTOR-BINDING AFFINITY

A series of new trypsin-like serine protease inhibitors, 1, 2 and 7-23 , containing amidinobenzene moiety was found to show potent LTB4-recep tor affinity. Among them, compounds 1 and 2 were found to be LTB4 rece ptor antagonists based on an inhibition assay of human polymorphonucle ar neutrophil (PMN) intracellular calcium mobilization induced by LTB4 . Compounds 1 and 2, which satisfy the reported structural requirement s for good oral activity, are expected to show a balanced dual mode of action, i.e., protease inhibitory activity and LTB4 receptor antagoni st activity, in vivo. (C) 1997 Elsevier Science Ltd.