1. The discovery of setileuton, a potent and selective 5-lipoxygenase inhibitor
- Author
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Richard Friesen, Frédéric Massé, Anne Châteauneuf, Yves Ducharme, Yves Gareau, Erich L. Grimm, Bruce Mackay, Myriam Salem, Sebastien Laliberte, Helene Juteau, Christine Brideau, Marc Ouellet, Marc Blouin, and Angela Styhler
- Subjects
business.industry ,Organic Chemistry ,Pharmacology ,Biochemistry ,Potassium channel ,Leukotriene biosynthesis ,Inhibitory potency ,In vivo ,Drug Discovery ,5-Lipoxygenase Inhibitor ,Medicine ,Setileuton ,business ,Gene - Abstract
The discovery of novel and selective inhibitors of human 5-lipoxygenase (5-LO) is described. These compounds are potent, orally bioavailable, and active at inhibiting leukotriene biosynthesis in vivo in a dog PK/PD model. A major focus of the optimization process was to reduce affinity for the human ether-a-go-go gene potassium channel while preserving inhibitory potency on 5-LO. These efforts led to the identification of inhibitor (S)-16 (MK-0633, setileuton), a compound selected for clinical development for the treatment of respiratory diseases.
- Published
- 2010