Discovery of a Novel Series of 7-Azaindole Scaffold Derivatives as PI3K Inhibitors with Potent Activity

  • ACS Med Chem Lett. 2017 Jul 26;8(8):875-880. doi: 10.1021/acsmedchemlett.7b00222.
Chengbin Yang  1 ,  Xi Zhang  2 ,  Yi Wang  2 ,  Yongtai Yang  1 ,  Xiaofeng Liu  1 ,  Mingli Deng  1 ,  Yu Jia  1 ,  Yun Ling  1 ,  Ling-Hua Meng  2 ,  Yaming Zhou  1
Affiliations
  • 1. Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China.
  • 2. Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
PMID: 28835805 DOI: 10.1021/acsmedchemlett.7b00222
Abstract

The phosphoinositide 3-kinase (PI3K) inhibitors potently inhibit the signaling pathway of PI3K/Akt/mTOR, which provides a promising new approach for the molecularly targeted Cancer therapy. In this work, a novel series of 7-azaindole scaffold derivatives was discovered by the fragment-based growing strategy. The structure-activity relationship profiles identified that the 7-azaindole scaffold derivatives exhibit potent activity against PI3K at molecular and cellular levels as well as cell proliferation in a panel of human tumor cells.

Keywords
1H-pyrrolo[2,3-b] pyridine; PI3K; PI3K/mTOR; cancer therapy; oncology.