title: Reduction of hERG inhibitory activity in the 4-piperidinyl urea series of H3 antagonists.
abstract: Structural features of the substituted 4-piperidinyl urea analogs 1, responsible for the H3 antagonist activity, have been identified. Structure-activity relationship of the H3 receptor affinity, hERG ion channel inhibitory activity and their separation is described. Preliminary pharmacokinetic evaluation of the compounds of the series is addressed.
authors.affiliation: Chemical Research, Cardiovascular/Metabolic Diseases and CNS Discovery, and Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, Kenilworth, NJ 07033, USA. michael.berlin@merck.com
authors.forename: Michael
authors.initials: M
authors.lastname: Berlin
authors.forename: Yoon Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Boyce
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Kevin D
authors.initials: KD
authors.lastname: McCormick
authors.forename: Steve
authors.initials: S
authors.lastname: Sorota
authors.forename: Shirley M
authors.initials: SM
authors.lastname: Williams
authors.forename: Robert E
authors.initials: RE
authors.lastname: West
authors.forename: Walter
authors.initials: W
authors.lastname: Korfmacher
mesh_terms: D000818:Animals; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006633:Histamine Antagonists / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D014508:Urea