title: Aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists--Increasing selectivity over hERG.
abstract: A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 microM.
authors.affiliation: Procter & Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, OH 45039, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Meyers
authors.forename: José L
authors.initials: JL
authors.lastname: Méndez-Andino
authors.forename: Anny-Odile
authors.initials: AO
authors.lastname: Colson
authors.forename: Namal C
authors.initials: NC
authors.lastname: Warshakoon
authors.forename: John A
authors.initials: JA
authors.lastname: Wos
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mitchell
authors.forename: Karen M
authors.initials: KM
authors.lastname: Hodge
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Howard
authors.forename: David C
authors.initials: DC
authors.lastname: Ackley
authors.forename: Jerry K
authors.initials: JK
authors.lastname: Holbert
authors.forename: Scott W
authors.initials: SW
authors.lastname: Mittelstadt
authors.forename: Martin E
authors.initials: ME
authors.lastname: Dowty
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Obringer
authors.forename: Ofer
authors.initials: O
authors.lastname: Reizes
authors.forename: X Eric
authors.initials: XE
authors.lastname: Hu
mesh_terms: D000818:Animals; D004285:Dogs; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007202:Indicators and Reagents; C000606913:KCNH2 protein, human; C103263:MCHR1 protein, human; D009281:Naphthalenes; D010879:Piperazines; D026902:Potassium Channel Blockers; D017481:Receptors, Somatostatin; C518531:aminomethyl tetrahydronaphthalene ketopiperazine