title: Synthesis and SAR study of potent and selective PI3Kδ inhibitors.
abstract: 2,3,4-Substituted quinolines such as (10a) were found to be potent inhibitors of PI3Kδ in both biochemical and cellular assays with good selectivity over three other class I PI3K isoforms. Some of those analogs showed favorable pharmacokinetic properties.
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Minna
authors: M
authors: Bui
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Xiaolin
authors: X
authors: Hao
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Youngsook
authors: Y
authors: Shin
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Mario
authors: M
authors: Cardozo
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Xiao
authors: X
authors: He
authors: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Kirk
authors: K
authors: Henne
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Julia
authors: J
authors: Suchomel
authors: Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: John
authors: J
authors: McCarter
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Lawrence R
authors: LR
authors: McGee
authors: Department of Inflammation Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Tisha
authors: T
authors: San Miguel
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Julio C
authors: JC
authors: Medina
authors: Department of Inflammation Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Deanna
authors: D
authors: Mohn
authors: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Thuy
authors: T
authors: Tran
authors: Department of Inflammation Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Sharon
authors: S
authors: Wannberg
authors: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Jamie
authors: J
authors: Wong
authors: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Simon
authors: S
authors: Wong
authors: Department of Inflammation Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Leeanne
authors: L
authors: Zalameda
authors: Department of Inflammation Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Daniela
authors: D
authors: Metz
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, United States.
authors: Timothy D
authors: TD
authors: Cushing
mesh_terms: D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D058534:Class I Phosphatidylinositol 3-Kinases
keywords: Autoimmune disorders; Inflammation; PI3Kδ; Reversed quinolines