title: 3-Nitro-4-amino benzoic acids and 6-amino nicotinic acids are highly selective agonists of GPR109b.
abstract: A series of 3-nitro-4-substituted-aminobenzoic acids were prepared and found to act as potent and highly selective agonists of the orphan human GPCR GPR109b, a low affinity receptor for niacin. No activity was observed at the closely homologous high affinity niacin receptor, GPR109a. A second series, comprising 6-amino-substituted nicotinic acids was, also prepared and several analogues showed comparable activity to the nitroaryl series.
authors.affiliation: Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. pskinner@arenapharm.com
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Skinner
authors.forename: Martin C
authors.initials: MC
authors.lastname: Cherrier
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Webb
authors.forename: Carleton R
authors.initials: CR
authors.lastname: Sage
authors.forename: Huong T
authors.initials: HT
authors.lastname: Dang
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Pride
authors.forename: Ruoping
authors.initials: R
authors.lastname: Chen
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Tamura
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Richman
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Connolly
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
mesh_terms: D000818:Animals; D001565:Benzoates / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009525:Niacin / Q000378:metabolism; D009539:Nicotinic Acids / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D001565:Benzoates; C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D009539:Nicotinic Acids; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin