Combs D W, Rampulla M S, Russell R K, Rampulla R A, Klaubert D H, Ritchie D, Meeks A S, Kirchner T
R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
Drug Des Deliv. 1990 Oct;6(4):241-54.
A synthetic program of rational drug design was undertaken to develop a series of quinazoline-3-oxides as pulmonary-selective inhibitors of ovalbumin-induced, leukotriene-mediated bronchoconstriction. The most active and selective compounds contained a methyl group at the 4-position, a medium sized branched alkyl group at the 2-position, and a small electron donating group on the phenyl ring. Significant enhancement in selectivity was observed in comparing the pulmonary versus cardiovascular effects of these new bronchodilators with the effects of theophylline.
