STRUCTURE-ACTIVITY-RELATIONSHIPS OF PYRIMIDO-PYRIMIDINE SERIES OF 5-LIPOXYGENASE INHIBITORS

A series of pyrimido-pyrimidine compounds were synthesized and a SAR s tudy was conducted for 5-LO inhibition using a broken cell preparation from RBL-1 cells. In this series compound 21 was found to be a potent 5-LO inhibitor in vitro. The enzyme 5-lipoxygenase (5-LO) catalyzes t he first step leading to the biosynthesis of leukotrienes from arachid onic acid.(1) Leukotrienes have been implicated as important mediators in a number of human diseases such as asthma, ulcerative colitis and allergic rhinitis.(2) Agents which inhibit 5-LO provide a useful thera peutic approach for these diseases as has been demonstrated by the lea ding clinical investigational drug zileuton.(3)