4,5-Dihydropyridazin-3-one derivatives as histamine H3 receptor inverse agonists

H3R structure–activity relationships for a new class of 4,5-dihydropyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modification of the 4,5-dihydropyridazinone moiety to block in vivo metabolism identified 4,4-dimethyl-6-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4,5-dihydr...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-01, Vol.22 (1), p.194-198
Hauptverfasser:	Hudkins, Robert L., Aimone, Lisa D., Dandu, Reddeppa reddy, Dunn, Derek, Gruner, John A., Huang, Zeqi, Josef, Kurt A., Lyons, Jacquelyn A., Mathiasen, Joanne R., Tao, Ming, Zulli, Allison L., Raddatz, Rita
Format:	Artikel
Sprache:	eng
Schlagworte:	4,5-Dihydropyridazin-3-one agonists Animals antagonists Area Under Curve Biological and medical sciences CEP-26401 Dose-Response Relationship, Drug Drug Design electroencephalography Electroencephalography - methods electromyography Electromyography - methods H3 inverse agonist histamine Histamine Agonists - chemical synthesis Histamine Agonists - pharmacology Histamine H3 receptor Kinetics Medical sciences metabolism Models, Chemical Pharmacology. Drug treatments Pyridazines - chemical synthesis Pyridazines - chemistry Pyridazines - pharmacology Rats receptors Receptors, Histamine H3 - chemistry Sleep-wake Stereoisomerism Structure-Activity Relationship structure-activity relationships Time Factors
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	H3R structure–activity relationships for a new class of 4,5-dihydropyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modification of the 4,5-dihydropyridazinone moiety to block in vivo metabolism identified 4,4-dimethyl-6-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4,5-dihydro-2H-pyridazin-3-one 22 as a lead candidate demonstrating potent in vivo functional H3R antagonism in the rat dipsogenia model and robust wake promoting activity in the rat EEG/EMG model.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.11.037