Discovery and bioactivity of 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl) morpholine derivatives as novel PI3K inhibitors.

Abstract

PI3K is a promising therapeutic target for cancer. With PI-103 as the lead compound, we designed and synthesized 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl)morpholine derivatives. 9, 10a, 10d, 10e had the IC(50) against PI3Kα comparable with PI-103. All of the compounds showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several cancer cell lines.

• Authors: Jia Wang, Xiang Wang, Yanhong Chen, Simeng Chen, Guang Chen, Linjiang Tong, Linghua Meng, Yuyuan Xie, Jian Ding, Chunhao Yang
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 1 Pg. 339-42 (Jan 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22130133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Furans
• Morpholines
• PI103
• Phosphoinositide-3 Kinase Inhibitors
• Pyridines
• Pyrimidines

Topics

• Antineoplastic Agents (pharmacology)
• Cell Cycle
• Cell Line, Tumor
• Cell Proliferation
• Drug Design
• Drug Screening Assays, Antitumor
• Enzyme Inhibitors (pharmacology)
• Furans (chemistry, pharmacology)
• Humans
• Inhibitory Concentration 50
• Morpholines (chemistry, pharmacology)
• Phosphatidylinositol 3-Kinases (chemistry)
• Phosphoinositide-3 Kinase Inhibitors
• Pyridines (chemistry, pharmacology)
• Pyrimidines (chemistry, pharmacology)