DISCOVERY OF L-740,515, A POTENT THIENOPYRIDINE CYSLT(1) RECEPTOR (LTD(4) RECEPTOR) ANTAGONIST

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