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Updated: May 25, 2026

Polygraphic Recording Procedure for Measuring Sleep in Mice
Published on: January 25, 2016
4-phenoxypiperidine pyridazin-3-one histamine H(3) receptor inverse agonists demonstrating potent and robust wake
Robert L Hudkins1, Allison L Zulli, Reddeppa reddy Dandu
1Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. rhudkins@cephalon.com
Abstract:
Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H(3)R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H(3)R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip.
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