title: From partial to full agonism: identification of a novel 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole as a full agonist of the human GPR119 receptor.
abstract: A novel GPR119 agonist based on the 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole scaffold was designed through lead optimization starting from pyrazole-based GPR119 agonist 1. The design is centered on the conformational restriction of the core scaffold, while minimizing the change in spatial relationships of two key pharmacophoric elements (piperidine-carbamate and aryl sulfone).
authors.affiliation: Pfizer Worldwide Research & Development, Groton Laboratories, Eastern Point Rd, Groton, CT 06340, United States. Kentaro.futatsugi@pfizer.com
authors.forename: Kentaro
authors.initials: K
authors.lastname: Futatsugi
authors.forename: Vincent
authors.initials: V
authors.lastname: Mascitti
authors.forename: Cristiano R W
authors.initials: CR
authors.lastname: Guimarães
authors.forename: Nao
authors.initials: N
authors.lastname: Morishita
authors.forename: Cuiman
authors.initials: C
authors.lastname: Cai
authors.forename: Michael P
authors.initials: MP
authors.lastname: DeNinno
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hamilton
authors.forename: Richard
authors.initials: R
authors.lastname: Hank
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Harris
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Kung
authors.forename: Sophie Y
authors.initials: SY
authors.lastname: Lavergne
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lefker
authors.forename: Michael G
authors.initials: MG
authors.lastname: Lopaze
authors.forename: Kim F
authors.initials: KF
authors.lastname: McClure
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Munchhof
authors.forename: Cathy
authors.initials: C
authors.lastname: Preville
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Robinson
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wright
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bonin
authors.forename: Peter
authors.initials: P
authors.lastname: Cornelius
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Amit S
authors.initials: AS
authors.lastname: Kalgutkar
mesh_terms: D002219:Carbamates / Q000737:chemistry; D006801:Humans; D010880:Piperidines / Q000737:chemistry; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; C519854:GPR119 protein, human; D010880:Piperidines; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; C031280:pyrazole; C032727:piperidine