title: Discovery and optimization of a series of 2-aminothiazole-oxazoles as potent phosphoinositide 3-kinase γ inhibitors.
abstract: A novel series of 2-aminothiazole-oxazoles was designed and synthesized as part of efforts to develop potent phosphoinositide 3-kinase γ (PI3Kγ) inhibitors. The modification of a high-throughput screening hit, compound 1, resulted in the identification of compounds 10 and 15, which displayed potent inhibitory activities in enzyme-based and cell-based assays.
authors.affiliation: Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403, Yoshino-Cho, Kita-Ku, Saitama-Shi, Saitama 331-9530, Japan. yusuke.oka@po.rd.taisho.co.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yabuuchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohtake
authors.forename: Shunichi
authors.initials: S
authors.lastname: Wakahara
authors.forename: Kayo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Endo
authors.forename: Yunoshin
authors.initials: Y
authors.lastname: Tamura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sekiguchi
mesh_terms: D000818:Animals; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000378:metabolism; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010080:Oxazoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D013844:Thiazoles; C004483:2-aminothiazole; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse