title: Aminopiperidine indazoles as orally efficacious melanin concentrating hormone receptor-1 antagonists.
abstract: The synthesis and biological evaluation of novel 3-amino indazole melanin concentrating hormone receptor-1 antagonists are reported, several of which demonstrated functional activity of less than 100nM. Compounds 19 and 28, two of the more potent compounds identified in this study, were characterized by high exposure in the brain and demonstrated robust efficacy when dosed in diet-induced obese mice.
authors.affiliation: Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Anil.Vasudevan@abbott.com
authors.forename: Anil
authors.initials: A
authors.lastname: Vasudevan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Souers
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Freeman
authors.forename: Mary K
authors.initials: MK
authors.lastname: Verzal
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Mulhern
authors.forename: Derek
authors.initials: D
authors.lastname: Wodka
authors.forename: John K
authors.initials: JK
authors.lastname: Lynch
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Engstrom
authors.forename: Seble H
authors.initials: SH
authors.lastname: Wagaw
authors.forename: Sevan
authors.initials: S
authors.lastname: Brodjian
authors.forename: Brian
authors.initials: B
authors.lastname: Dayton
authors.forename: Doug H
authors.initials: DH
authors.lastname: Falls
authors.forename: Eugene
authors.initials: E
authors.lastname: Bush
authors.forename: Michael
authors.initials: M
authors.lastname: Brune
authors.forename: Robin D
authors.initials: RD
authors.lastname: Shapiro
authors.forename: Kennan C
authors.initials: KC
authors.lastname: Marsh
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hernandez
authors.forename: Christine A
authors.initials: CA
authors.lastname: Collins
authors.forename: Philip R
authors.initials: PR
authors.lastname: Kym
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D010880:Piperidines / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
chemical_list: D019440:Anti-Obesity Agents; D007191:Indazoles; C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin; C032727:piperidine