title: Discovery of a series of potent arylthiadiazole H(3) antagonists.
abstract: A series of 2-piperidinopiperidine-5-arylthiadiazoles was synthesized and subjected to a structure-activity relationship (SAR) investigation. The potency of this series was improved to the single digit nanomolar range. The key analogs were shown to be free of P450 issues, and they also maintained good ex vivo activity and brain penetration.
authors.affiliation: Chemical Research Department, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. dong.xiao@merck.com
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: Michael
authors.initials: M
authors.lastname: Sofolarides
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Henry
authors.initials: H
authors.lastname: Vaccaro
authors.forename: Liwu
authors.initials: L
authors.lastname: Hong
authors.forename: Brian
authors.initials: B
authors.lastname: McKittrick
authors.forename: Robert E
authors.initials: RE
authors.lastname: West
authors.forename: Shirley M
authors.initials: SM
authors.lastname: Williams
authors.forename: Ren-Long
authors.initials: RL
authors.lastname: Wu
authors.forename: Joyce
authors.initials: J
authors.lastname: Hwa
authors.forename: Christopher
authors.initials: C
authors.lastname: Sondey
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006633:Histamine Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D013830:Thiadiazoles