2. Academic Validation
  3. Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment

Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment

  • Eur J Med Chem. 2021 Apr 5:215:113273. doi: 10.1016/j.ejmech.2021.113273.
Jianqing Zhang 1,  Pengqin Chen 2,  Yongli Duan 3,  Hehua Xiong 4,  Hongmin Li 5,  Yao Zeng 5,  Guang Liang 2,  Qidong Tang 6,  Di Wu 7
Affiliations

Affiliations

  • 1 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China; Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China.
  • 2 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China.
  • 3 School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China (UESTC), Chengdu, 610054, PR China.
  • 4 State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
  • 5 Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China.
  • 6 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China; Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China. Electronic address: tangqidongcn@126.com.
  • 7 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China. Electronic address: wudi2017@wmu.edu.cn.
PMID: 33601310 DOI: 10.1016/j.ejmech.2021.113273
Abstract

In this study, a series of pyrrolo [2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment were synthesized and their biological activity were tested. Most of the target compounds displayed moderate to excellent activity against one or more Cancer cell lines and low activity against human normal cell LO2 in vitro. The most promising compound 51, of which the IC50 values were 0.66 μM, 0.38 μM and 0.44 μM against cell lines A549, Hela and MCF-7, shown more remarkable activity and better Apoptosis effect than the positive control Cabozantinib. The structure-activity relationships (SARs) indicated that double-EWGs (such as R3 = 2-Cl-4-CF3) on the terminal phenyl rings was a key factor in improving the biological activity. In addition, the further research on compound 51 mainly included c-Met kinase activity and selectivity, concentration dependence, and molecular docking.

Keywords

1,8-Naphthyridine-4-one; 7H-pyrrolo[2,3-d]pyrimidine; Activity; Inhibitors; SAR; Synthesis.

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