Identification of pyridazin-3-one derivatives as potent, selective histamine H₃ receptor inverse agonists with robust wake activity

Autor:	Robert L, Hudkins, Lisa D, Aimone, Thomas R, Bailey, Robert J, Bendesky, Reddeppa Reddy, Dandu, Derek, Dunn, John A, Gruner, Kurt A, Josef, Yin-Guo, Lin, Jacquelyn, Lyons, Val R, Marcy, Joanne R, Mathiasen, Babu G, Sundar, Ming, Tao, Allison L, Zulli, Rita, Raddatz, Edward R, Bacon
Rok vydání:	2011
Předmět:	Male Dose-Response Relationship Drug Molecular Structure Drinking Stereoisomerism Rats Histamine Agonists Pyridazines Disease Models Animal Structure-Activity Relationship Animals Humans Receptors Histamine H3 Wakefulness
Zdroj:	Bioorganicmedicinal chemistry letters. 21(18)
ISSN:	1464-3405
Popis:	H(3)R structure-activity relationships on a novel class of pyridazin-3-one H(3)R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H(3)R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::751b027788338fa7af0c76f12a30b863 https://pubmed.ncbi.nlm.nih.gov/21782432 Zobrazit plný text záznamu Full Text from ScienceDirect