The Discovery of Setileuton, a Potent and Selective 5-Lipoxygenase Inhibitor
- 13 April 2010
- journal article
- Published by American Chemical Society (ACS) in ACS Medicinal Chemistry Letters
- Vol. 1 (4), 170-174
- https://doi.org/10.1021/ml100029k
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.Keywords
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