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

Jia Wang; Xiang Wang; Yanhong Chen; Simeng Chen; Guang Chen; Linjiang Tong; Linghua Meng; Yuyuan Xie; Jian Ding; Chunhao Yang

doi:10.1016/j.bmcl.2011.11.003

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

Bioorg Med Chem Lett. 2012 Jan 1;22(1):339-42. doi: 10.1016/j.bmcl.2011.11.003. Epub 2011 Nov 9.

Authors

Jia Wang¹, Xiang Wang, Yanhong Chen, Simeng Chen, Guang Chen, Linjiang Tong, Linghua Meng, Yuyuan Xie, Jian Ding, Chunhao Yang

Affiliation

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China.

PMID: 22130133
DOI: 10.1016/j.bmcl.2011.11.003

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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