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

Novel 2-aminothiazole-oxazoles were synthesized and evaluated as phosphoinositide 3-kinase γ (PI3Kγ) inhibitors. 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-thr...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-12, Vol.22 (24), p.7534-7538
Hauptverfasser:	Oka, Yusuke, Yabuuchi, Tetsuya, Fujii, Yasuyuki, Ohtake, Hidenori, Wakahara, Shunichi, Matsumoto, Kayo, Endo, Mayumi, Tamura, Yunoshin, Sekiguchi, Yoshinori
Format:	Artikel
Sprache:	eng
Schlagworte:	2-Aminothiazole-oxazoles Animals Biological and medical sciences chemistry Class Ib Phosphatidylinositol 3-Kinase - antagonists & inhibitors 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 Medical sciences Mice Models, Molecular Molecular Structure Oxazoles - chemistry Oxazoles - pharmacology Pharmacology. Drug treatments phosphatidylinositol 3-kinase Phosphoinositide 3-kinase PI3Kγ inhibitor Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology screening Structure-Activity Relationship Thiazoles - chemistry Thiazoles - pharmacology
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Zusammenfassung:	Novel 2-aminothiazole-oxazoles were synthesized and evaluated as phosphoinositide 3-kinase γ (PI3Kγ) inhibitors. 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2012.10.028