The emergence of potent and selective peptide leukotriene receptor antagonists

Leukotriene (LT) C4, LTD4 and LTE4 collectively comprise the constituents of slow reacting substance of anaphylaxis. Based on their well-documented physiology, and a substantial body of circumstantial evidence, it has been hypothesized that they may be etiologic in allergic diseases, including asthma. Using various chemical approaches, a variety of chemically distinct, highly potent and selective LT antagonists have been disclosed including SKF 104,353, ICI 198,615, L 660,711 and WY 48,252. All are, or will soon, enter clinical trials for asthma. These compounds should provide a viable test for the hypothesis that LTs are etiologic in asthma. The complexity of the disease suggests that clinical expectations for these compounds, or any single entity, should be moderate.