title: Discovery and optimization of N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamides as novel GPR119 agonists.
abstract: The discovery and optimization of novel N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamide GPR119 agonists is described. Modification of the pyridylphthalimide motif of the molecule with R(1)=-Me and R(2)=-(i)Pr substituents, incorporated with a 6-fluoro substitution on the central phenyl ring offered a potent and metabolically stable tool compound 22.
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: yum@amgen.com.
authors: Ming
authors: M
authors: Yu
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Jian
authors: J
authors: Ken Zhang
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Yingcai
authors: Y
authors: Wang
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Jiang
authors: J
authors: Zhu
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Frank
authors: F
authors: Kayser
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Julio C
authors: JC
authors: Medina
authors: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Karen
authors: K
authors: Siegler
authors: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Marion
authors: M
authors: Conn
authors: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Bei
authors: B
authors: Shan
authors: Department of Pharmacokinetics & Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Mark P
authors: MP
authors: Grillo
authors: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Peter
authors: P
authors: Coward
authors: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Jiwen
authors: J
authors: Jim Liu
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; C519854:GPR119 protein, human; C588335:N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo(3,4-c)pyridin-4-yloxy)phenyl)benzenesulfonamide; D000096926:Benzenesulfonamides
keywords: Agonist; GPR119; Type 2 diabetes