Synthesis and biochemical/pharmacological profile of the novel leukotriene B4 receptor antagonist sodium (1S*, 3S*)-1-hydroxy-3-[(3 R*S*,E)-3-hydroxy-7-phenyl-1-hepten-1-yl]-1-cyclohexane acetate.

A novel series of leukotriene B4 (LTB4) antagonists is reported. These compounds present a cyclohexane ring in their chemical structure, which mimics the three conjugated double bonds of LTB4. The biochemical/pharmacological profile of the leader compound, PH-163 (sodium (1S*,3S*)-1-hydroxy-3-[(3R*S,E)-3-hydroxy-7-phenyl-1-hepten-1-yl]- 1 -cyclohexane acetate, CAS 163251-41-0) is described. This compound competes with [3H]LTB4 binding to its receptor in human neutrophils and guinea pig lung membranes with IC50's of 0.8 mumol/l and 0.2 mumol/l, respectively, i.e. relative binding affinities of 1% as compared to LTB4. PH-163 does not elicit any agonist activity, but inhibits leucocyte chemotaxis induced by LTB4 (pKB = 6.57) and lung parenchymal strip contraction (IC50 = 0.1 mumol/l). In conclusion, PH-163 or derivatives could be useful in the treatment of inflammatory diseases where LTB4 seems to be involved.