title: Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity.
abstract: A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor 1 (MCHr1) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkylamine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series.
authors.affiliation: Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. andrew.judd@abbott.com
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Judd
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Souers
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wodka
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Mulhern
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Iyengar
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
authors.forename: John K
authors.initials: JK
authors.lastname: Lynch
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Freeman
authors.forename: H Douglas
authors.initials: HD
authors.lastname: Falls
authors.forename: Sevan
authors.initials: S
authors.lastname: Brodjian
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dayton
authors.forename: Regina M
authors.initials: RM
authors.lastname: Reilly
authors.forename: Gary
authors.initials: G
authors.lastname: Gintant
authors.forename: James T
authors.initials: JT
authors.lastname: Limberis
authors.forename: Ann
authors.initials: A
authors.lastname: Mikhail
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Leitza
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Houseman
authors.forename: Gilbert
authors.initials: G
authors.lastname: Diaz
authors.forename: Eugene N
authors.initials: EN
authors.lastname: Bush
authors.forename: Robin
authors.initials: R
authors.lastname: Shapiro
authors.forename: Victoria
authors.initials: V
authors.lastname: Knourek-Segel
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hernandez
authors.forename: Kennan C
authors.initials: KC
authors.lastname: Marsh
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Christine A
authors.initials: CA
authors.lastname: Collins
authors.forename: Philip R
authors.initials: PR
authors.lastname: Kym
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002867:Chromones / Q000494:pharmacology*; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D018408:Patch-Clamp Techniques; D010599:Pharmacokinetics; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D002867:Chromones; D051638:Ether-A-Go-Go Potassium Channels; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor