ETHYL]-3-(2-PHENYLETHOXY)-2-PYRIDINYL]-2-PROPENOIC ACID - A HIGH-AFFINITY LEUKOTRIENE B-4 RECEPTOR ANTAGONIST WITH ORAL ANTIINFLAMMATORY ACTIVITY

An extensive structure-activity study based around the high-affinity l eukotriene B-4 (LTB(4)) receptor antagonist SB 201146 (1) led to the i dentification of ethyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic ac id (3). This compound displays high affinity for the human neutrophil LTB(4) receptor (K-i = 0.78 nM), blocks LTB(4)-induced Ca2+ mobilizati on with an IC50 of 6.6 +/- 1.5 nM, and demonstrates potent oral and to pical antiinflammatory activity in a murine model of dermal inflammati on.