title: Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity.
abstract: A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test.
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA. Electronic address: manuel.ruiz@merck.com.
authors.forename: Manuel
authors.initials: M
authors.lastname: de Lera Ruiz
authors.forename: Junying
authors.initials: J
authors.lastname: Zheng
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Berlin
authors.forename: Kevin D
authors.initials: KD
authors.lastname: McCormick
authors.forename: Robert G
authors.initials: RG
authors.lastname: Aslanian
authors.forename: Robert
authors.initials: R
authors.lastname: West
authors.forename: Joyce
authors.initials: J
authors.lastname: Hwa
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
authors.forename: Margaret
authors.initials: M
authors.lastname: van Heek
mesh_terms: D000818:Animals; D054828:Histamine H3 Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism
chemical_list: D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3
keywords: H3 antagonists; Histamine