Discovery and optimization of a series of 2-aminothiazole-oxazoles as potent phosphoinositide 3-kinase γ inhibitors

Yusuke Oka; Tetsuya Yabuuchi; Yasuyuki Fujii; Hidenori Ohtake; Shunichi Wakahara; Kayo Matsumoto; Mayumi Endo; Yunoshin Tamura; Yoshinori Sekiguchi

doi:10.1016/j.bmcl.2012.10.028

Discovery and optimization of a series of 2-aminothiazole-oxazoles as potent phosphoinositide 3-kinase γ inhibitors

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7534-8. doi: 10.1016/j.bmcl.2012.10.028. Epub 2012 Oct 12.

Authors

Yusuke Oka¹, Tetsuya Yabuuchi, Yasuyuki Fujii, Hidenori Ohtake, Shunichi Wakahara, Kayo Matsumoto, Mayumi Endo, Yunoshin Tamura, Yoshinori Sekiguchi

Affiliation

¹ 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

PMID: 23122859
DOI: 10.1016/j.bmcl.2012.10.028

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.

MeSH terms

Animals
Class Ib Phosphatidylinositol 3-Kinase / metabolism
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Discovery*
High-Throughput Screening Assays
Macrophages / drug effects
Macrophages / enzymology
Macrophages / metabolism
Mice
Models, Molecular
Molecular Structure
Oxazoles / chemistry
Oxazoles / pharmacology*
Phosphoinositide-3 Kinase Inhibitors*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Oxazoles
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors
Thiazoles
2-aminothiazole
Class Ib Phosphatidylinositol 3-Kinase
Pik3cg protein, mouse