Design, synthesis and bronchodilatory activity of a series of quinazoline-3-oxides.
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.
Combs
D W
DW
R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
Rampulla
M S
MS
Russell
R K
RK
Rampulla
R A
RA
Klaubert
D H
DH
Ritchie
D
D
Meeks
A S
AS
Kirchner
T
T
D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000517:prevention & control; D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D015195:Drug Design; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D015289:Leukotrienes / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010862:Pilocarpine / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D001993:Bronchodilator Agents; D015289:Leukotrienes; D011799:Quinazolines; D010862:Pilocarpine; D010047:Ovalbumin; D013806:Theophylline