title: Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
abstract: A series of urea-based N-1-(2-aminoethyl)-indazoles was synthesized and evaluated for melanin-concentrating hormone receptor 1 (MCHr1) antagonism in both binding and functional assays. Several compounds that acted as MCHr1 antagonists were identified, and optimization afforded a compound with excellent binding affinity, good functional potency, and oral efficacy in a chronic model for weight loss in diet-induced obese mice.
authors.affiliation: Metabolic Disease Research, Abbott Laboratories, Abbott Park, IL 60064, USA. andrew.souers@abbott.com
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Souers
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wodka
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Judd
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Mulhern
authors.forename: James J
authors.initials: JJ
authors.lastname: Napier
authors.forename: Michael E
authors.initials: ME
authors.lastname: Brune
authors.forename: Eugene N
authors.initials: EN
authors.lastname: Bush
authors.forename: Sevan J
authors.initials: SJ
authors.lastname: Brodjian
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dayton
authors.forename: Robin
authors.initials: R
authors.lastname: Shapiro
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: D000818:Animals; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry*
chemical_list: D007191:Indazoles; C491209:Mchr1 protein, mouse; D017481:Receptors, Somatostatin; D014508:Urea