title: Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: impacting hERG liability via aryl modifications.
abstract: Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. mark.mcbriar@spcorp.com
authors.forename: Mark D
authors.initials: MD
authors.lastname: McBriar
authors.forename: Henry
authors.initials: H
authors.lastname: Guzik
authors.forename: Sherry
authors.initials: S
authors.lastname: Shapiro
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Paruchova
authors.forename: John W
authors.initials: JW
authors.lastname: Clader
authors.forename: Kim
authors.initials: K
authors.lastname: O'neill
authors.forename: Brian
authors.initials: B
authors.lastname: Hawes
authors.forename: Steve
authors.initials: S
authors.lastname: Sorota
authors.forename: Michael
authors.initials: M
authors.lastname: Margulis
authors.forename: Kristal
authors.initials: K
authors.lastname: Tucker
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weston
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cox
mesh_terms: D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008543:Melanins / Q000737:chemistry*; D008956:Models, Chemical; D011485:Protein Binding; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D014508:Urea / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; C103263:MCHR1 protein, human; D008543:Melanins; D017481:Receptors, Somatostatin; D014508:Urea