title: Synthesis and evaluation of pyridazinone-phenethylamine derivatives as selective and orally bioavailable histamine H3 receptor antagonists with robust wake-promoting activity.
abstract: A series of pyridazinone-phenethylamine derivatives with moderate to low nanomolar affinity for rat and human H(3)R are described. These analogs exhibited excellent selectivity and metabolic stability, with acceptable rat pharmacokinetic properties. In vivo, 7 and 11 demonstrated potent H(3)R functional antagonism in the rat dipsogenia model and robust wake-promoting activity in the rat electroencephalogram/electromyography (EEG/EMG) model.
authors.affiliation: Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. rdandu@cephalon.com
authors.forename: Reddeppa Reddy
authors.initials: RR
authors.lastname: Dandu
authors.forename: John A
authors.initials: JA
authors.lastname: Gruner
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Mathiasen
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Aimone
authors.forename: Greg
authors.initials: G
authors.lastname: Hostetler
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Benfield
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bendesky
authors.forename: Val R
authors.initials: VR
authors.lastname: Marcy
authors.forename: Rita
authors.initials: R
authors.lastname: Raddatz
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hudkins
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004569:Electroencephalography; D004576:Electromyography; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D054828:Histamine H3 Antagonists