2. Academic Validation
  3. Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

  • Eur J Med Chem. 2021 Aug 5:220:113497. doi: 10.1016/j.ejmech.2021.113497.
Dandan Xu 1,  Deqiao Sun 2,  Wei Wang 1,  Xia Peng 3,  Zhengsheng Zhan 4,  Yinchun Ji 3,  Yanyan Shen 3,  Meiyu Geng 2,  Jing Ai 5,  Wenhu Duan 6
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
  • 2 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China; School of Life Science and Technology, Shanghai Tech University, 393 Middle Huaxia Road, Pudong New District, Shanghai, 201210, China.
  • 3 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China.
  • 4 Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China.
  • 5 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China; Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Xiangshan Branch Lane, Xihu District, Hangzhou, 330106, China. Electronic address: jai@simm.ac.cn.
  • 6 Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China. Electronic address: whduan@simm.ac.cn.
PMID: 33957388 DOI: 10.1016/j.ejmech.2021.113497
Abstract

Axl has emerged as an attractive target for Cancer therapy due to its strong correlation with tumor growth, metastasis, poor survival, and drug resistance. Herein, we report the design, synthesis and structure-activity relationship (SAR) investigation of a series of pyrrolo[2,3-d]pyrimidine derivatives as new Axl inhibitors. Among them, the most promising compound 13b showed high enzymatic and cellular Axl potencies. Furthermore, 13b possessed preferable pharmacokinetic properties and displayed promising therapeutic effect in BaF3/TEL-Axl xenograft tumor model. Compound 13b may serve as a lead compound for new antitumor drug discovery.

Keywords

Axl; Cancer; Inhibitor; Pyrrolo[2,3-d]pyrimidine.

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