title: Design and evaluation of a 2-(2,3,6-trifluorophenyl)acetamide derivative as an agonist of the GPR119 receptor.
abstract: The design and synthesis of a GPR119 agonist bearing a 2-(2,3,6-trifluorophenyl)acetamide group is described. The design capitalized on the conformational restriction found in N-β-fluoroethylamide derivatives to help maintain good levels of potency while driving down both lipophilicity and oxidative metabolism in human liver microsomes. The chemical stability and bioactivation potential are discussed.
authors.affiliation: Pfizer Global Research & Development, Groton, CT 06340, USA. vincent.mascitti@pfizer.com
authors.forename: Vincent
authors.initials: V
authors.lastname: Mascitti
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Stevens
authors.forename: Chulho
authors.initials: C
authors.lastname: Choi
authors.forename: Kim F
authors.initials: KF
authors.lastname: McClure
authors.forename: Cristiano R W
authors.initials: CR
authors.lastname: Guimarães
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Farley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Munchhof
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Robinson
authors.forename: Kentaro
authors.initials: K
authors.lastname: Futatsugi
authors.forename: Sophie Y
authors.initials: SY
authors.lastname: Lavergne
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lefker
authors.forename: Peter
authors.initials: P
authors.lastname: Cornelius
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bonin
authors.forename: Amit S
authors.initials: AS
authors.lastname: Kalgutkar
authors.forename: Raman
authors.initials: R
authors.lastname: Sharma
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry
chemical_list: D000081:Acetamides; C519854:GPR119 protein, human; D043562:Receptors, G-Protein-Coupled