2. Academic Validation
  3. Design, synthesis and biological evaluation of novel 3H-imidazole [4,5-b] pyridine derivatives as selective mTOR inhibitors

Design, synthesis and biological evaluation of novel 3H-imidazole [4,5-b] pyridine derivatives as selective mTOR inhibitors

  • Bioorg Med Chem Lett. 2017 Aug 1;27(15):3395-3398. doi: 10.1016/j.bmcl.2017.06.010.
Lingzhi Zhang 1,  Tantan Bu 1,  Xiaobo Bao 2,  Tingting Liang 2,  Yiran Ge 3,  Yungen Xu 4,  Qihua Zhu 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
  • 2 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
  • 3 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
  • 4 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China. Electronic address: xu_yungen@hotmail.com.
  • 5 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China. Electronic address: zhuqihua@vip.126.com.
PMID: 28633896 DOI: 10.1016/j.bmcl.2017.06.010
Abstract

A series of 3H-imidazo [4,5-b] pyridines derivatives were designed and synthesized as selective mTOR inhibitors. The systematic optimization of the molecules resulted in the identification of two compounds 10d and 10n with nanomolar mTOR inhibitory activity and selectivity over PI3Kα. Besides, compounds 10d and 10n demonstrated attractive potency against human breast Cancer cells (MCF-7) and human ovarian Cancer cell (A2780).

Keywords

3H-Imidazo [4,5-b] pyridine; Antitumor; Mammalian target of rapamycin; Synthesis; mTOR inhibitors.

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