In the lecture I will describe first the basic biology that lead to the hypothesis that inhibiting the synthesis or the activity of leukotrienes would be useful for the treatment of asthma. I will then describe how we discovered our first lead molecules. Optimization of our initial leads lead to our first clinical candidate MK571. MK571 was progressed to clinical studies which showed that inhibition of the effects of leukotrienes would be useful for the treatment of asthma. Unfortunately high dose studies in mice gave unexpected toxicity and the development of MK571 was stopped.. Further modifications and clinical studies lead to Singulair which went on the market in 1997.
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