Am. J. Respir. Crit. Care Med.,
Volume 157, Number 6, June 1998, S220-S226
Chemistry and Structure-Activity Relationships of
Leukotriene Receptor Antagonists
PETER R.
BERNSTEIN
Zeneca Pharmaceuticals, Wilmington, Delaware
Several strategies have been employed by medicinal chemists in the design of potent and selective
leukotriene receptor antagonists
leukotriene structural analogs, FPL 55712 analogs, and random
screening of corporate compound banks. Lead compounds were optimized, often through the exchange of ideas with groups working on other chemical series of leukotriene antagonists. Pranlukast
can likely be traced to a lead compound identified by random screening that was initially modified by
incorporating structural components present in FPL 55712. Montelukast originated from an early
quinoline lead, which was modified with leukotriene structural elements. Zafirlukast is based on a
lead compound that incorporated structural components from both FPL 55712 and the leukotrienes.
Therefore, each medicinal chemistry strategy that was originally employed has successfully identified
clinically effective leukotriene receptor antagonists. Bernstein PR. Chemistry and structure-activity relationships of leukotriene receptor antagonists.
