SYNTHESIS AND BIOCHEMICAL PHARMACOLOGICAL PROFILE OF THE NOVEL LEUKOTRIENE B-4, RECEPTOR ANTAGONIST SODIUM K,E)-3-HYDROXY-PHENYL-1-HEPTEN-1-YL]-1-CYCLOHEXANE ACETATE/

A novel series of leukotriene B-4 (LTB(4)) antagonists is reported. Th ese compounds present a cyclohexane ring in their chemical structure, which mimics the three conjugated double bonds of LTB(4). The biochemi cal/pharmacological profile of the leader compound, PH-163 (sodium E)- 3-hydroxy-7-phenyl-1-hepten-1-yl]-1-cyclohexane acetate, CAS 163251-41 -0) is described. This compound competes with [H-3]LTB(4) binding to i ts receptor in human neutrophils and guinea pig lung membranes with IC 50's of 0.8 mu mol/l and 0.2 mu mol/l, respectively, i.e. relative bin ding affinities of 1 % as compared to LTB(4). PH-163 does not elicit a ny agonist activity, but inhibits leucocyte chemotaxis induced by LTB( 4) (pK(B) = 6.57) and lung parenchymal strip contraction (IC50 = 0.1 m u mol/l). In conclusion, PH-163 or derivatives could be useful in the treatment of inflammatory diseases where LTB(4) seems to be involved.