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Structure-activity studies leading to the discovery of a new series of non-quinoline cysLT 1 receptor (LTD 4 receptor) antagonists are described. These studies demonstrated that the quinoline ring system of montelukast ( 5 ) may be replaced by an appropriately substituted thienopyridine system, yielding potent compounds. Two other molecular features of montelukast, the terminal phenyl ring substitution and the vinyl link, were also reevaluated. These studies led to the identification of 1 (L-740,515) , a compound with optimized in vitro and in vivo biological profiles.

A new class of potent ligand for the human peripheral cannabinoid (hCB 2 ) receptor is described. Two indole analogs 13 and 17 exhibited nanomolar potencies (K i ) with good selectivity for the hCB 2 receptor over the human central cannabinoid (hCB 1 ) receptor.

Analogues of PGE(2) wherein the hydroxycyclopentanone ring has been replaced by a lactam have been prepared and evaluated as ligands for the EP(4) receptor. An optimized compound (19a) shows high potency and agonist efficacy at the EP(4) receptor and is highly selective over the other seven known prostaglandin receptors.