title: Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b.
abstract: Recently identified GPCRs, GPR109a and GPR109b, the high and low affinity receptors for niacin, may represent good targets for the development of HDL elevating drugs for the treatment of atherosclerosis. Acifran, an agonist of both receptors, has been tested in human subjects, yet until recently very few analogs had been reported. We describe a series of acifran analogs prepared using newly developed synthetic pathways and evaluated as agonists for GPR109a and GPR109b, resulting in identification of compounds with improved activity at these receptors.
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, California 92121, USA.
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Jung
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Johnson
authors.forename: Tracy
authors.initials: T
authors.lastname: Duong
authors.forename: Marc
authors.initials: M
authors.lastname: Decaire
authors.forename: Jane
authors.initials: J
authors.lastname: Uy
authors.forename: Tawfik
authors.initials: T
authors.lastname: Gharbaoui
authors.forename: P Douglas
authors.initials: PD
authors.lastname: Boatman
authors.forename: Carleton R
authors.initials: CR
authors.lastname: Sage
authors.forename: Ruoping
authors.initials: R
authors.lastname: Chen
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: D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009525:Niacin / Q000378:metabolism* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin; C036804:acifran; D000242:Cyclic AMP