Leukotriene receptor antagonists. III. Pharmacological and chemical studies with LY137617, a leukotriene D4 and leukotriene E4 receptor antagonist.

A series of chlorophenoxyalkyl acids were prepared and evaluated as pharmacological antagonists of leukotriene D4. Structure-activity relationship studies pointed to LY137617 as a compound with possible therapeutic value. In experiments on isolated smooth muscles from the guinea-pig, this agent was a selective and moderately potent antagonist of leukotriene D4 and also leukotriene E4. Other in vitro experiments demonstrated that LY137617 had a high affinity for protein molecules. This was reflected in vivo as a weaker than expected efficacy against leukotriene-mediated events, limiting the compound's potential as a clinical candidate. Nevertheless, agents of this type will prove useful in the laboratory to increase knowledge of leukotriene receptor-antagonist interactions.