Structure-activity relationships (SAR) of the 3-alkyl substituents among a series of hydroxy-acetophenone leukotriene antagonists.

LY171883 is an orally active antagonist of leukotriene (LT) D4 and LTE4. A series of related compounds varying the position and nature of the alkyl side chain were synthesized and evaluated for their ability to block LTD4-induced contraction of guinea pig ileum. Maximal activity was obtained with n-propyl, n-butyl, and n-pentyl substituents with slightly reduced activity for longer side chains. Polar groups on the side chain substantially reduced activity. Thus, it appears that the leukotriene receptor site requires a nonpolar alkyl group of moderate size at the 3-position on this type of receptor antagonist.