title: An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists.
abstract: The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG separation, CYP3A4 profile, and receptor cross-reactivity profiles.
authors.affiliation: Metabolic Disease Research, Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. rajesh.iyengar@abbott.com
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Iyengar
authors.forename: John K
authors.initials: JK
authors.lastname: Lynch
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Mulhern
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Judd
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Freeman
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Souers
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wodka
authors.forename: H
authors.initials: H
authors.lastname: Doug 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: Sue
authors.initials: S
authors.lastname: Swanson
authors.forename: Zhi
authors.initials: Z
authors.lastname: Su
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Martin
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: Christine A
authors.initials: CA
authors.lastname: Collins
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Philip R
authors.initials: PR
authors.lastname: Kym
mesh_terms: D000478:Alkylation; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002867:Chromones; D003429:Cross Reactions; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D051638:Ether-A-Go-Go Potassium Channels / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002867:Chromones; D065607:Cytochrome P-450 Enzyme Inhibitors; D000072237:ERG1 Potassium Channel; D004791:Enzyme Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; D006571:Heterocyclic Compounds; C000606913:KCNH2 protein, human; C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human