title: Agonist lead identification for the high affinity niacin receptor GPR109a.
abstract: A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, San Diego, CA 92121, USA.
authors.forename: Tawfik
authors.initials: T
authors.lastname: Gharbaoui
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Skinner
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Shin
authors.forename: Claudia
authors.initials: C
authors.lastname: Averbuj
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: Martin C
authors.initials: MC
authors.lastname: Cherrier
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Webb
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Tamura
authors.forename: Ning
authors.initials: N
authors.lastname: Zou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rodriguez
authors.forename: P Douglas
authors.initials: PD
authors.lastname: Boatman
authors.forename: Carleton R
authors.initials: CR
authors.lastname: Sage
authors.forename: Andrew
authors.initials: A
authors.lastname: Lindstrom
authors.forename: Jerry
authors.initials: J
authors.lastname: Xu
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Schrader
authors.forename: Brian M
authors.initials: BM
authors.lastname: Smith
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: Steven L
authors.initials: SL
authors.lastname: Colletti
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
mesh_terms: D000147:Acids, Heterocyclic / Q000737:chemistry*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D009525:Niacin / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry*; D011978:Receptors, Nicotinic / Q000737:chemistry*; D013154:Spleen / Q000378:metabolism
chemical_list: D000147:Acids, Heterocyclic; C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin; D000242:Cyclic AMP