Synthesis and biological activity of fused furo[2,3-d]pyrimidinone derivatives as analgesic and antitumor agents

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• 作者：Qing Li ; Yong-Mei Chen ; Yang-Gen Hu ; Xin Luo…
• 关键词：Fused furo[2 ; 3 ; d]pyrimidinone derivatives ; Synthesis ; Analgesic and antitumor
• 刊名：Research on Chemical Intermediates
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：42
• 期：2
• 页码：939-949
• 全文大小：427 KB
• 参考文献：1.Y.-G. Hu, Y. Wang, S.-M. Du, X.-B. Chen, M.-W. Ding, Efficient synthesis and biological evaluation of some 2,4-diamino-furo[2,3-d]pyrimidine derivatives. Bioorg. Med. Chem. Lett. 20, 6188–6190 (2010)CrossRef
  2.Y.-G. Hu, H. Gao, G. Wang, Y. Wang, Y. Qu, J. Xu, Synthesis and antitumor activity of some 2-amino-furo[2,3-d]pyrimidin-4(3h)-one derivatives. Chin. J. Org. Chem. 32, 1468–1472 (2012)CrossRef
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  9.Y.-G. Hu, M. Liu, M.-W. Ding, Efficient synthesis of new tetracyclic benzofuro[3,2-d] imidazo[1,2-a]pyrimidine-2,5-(1H,3H)-diones. Chin. J. Chem. 28, 309–312 (2010)CrossRef
  10.Y.-G. Hu, M.-G. Liu, M.-W. Ding, Efficient iminophosphorane mediated preparation of benzofuro[3, 2-d]pyrimidin-4(3H)-ones and unexpected ring opening products. Helv. Chim. Acta 91, 862–872 (2008)CrossRef
  11.Y.-G. Hu, S.-M. Du, Q. Li, M.-W. Ding, Synthesis and crystal structure of 1-(4-Fluorophenyl)- 2-hexyl- thiobenzo[4, 5]-furo[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin- 5(1H)- one. Chin. J. Struct. Chem. 30, 75–78 (2011)
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• 作者单位：Qing Li (1) (2)
  Yong-Mei Chen (3)
  Yang-Gen Hu (1) (2)
  Xin Luo (4)
  Joshua Ka Shun Ko (5)
  Chi Wai Cheung (4)
  
  1. Department of Anesthesiology, Institute of Anesthesiology, Taihe Hospital of Hubei University of Medicine, Shiyan, 442000, China
  2. Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry, Hubei University of Medicine, Shiyan, 442000, China
  3. Department of Medical Laboratory Science, Taihe Hospital of Hubei University of Medicine, Shiyan, 442000, China
  4. Department of Anaesthesiology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China
  5. Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 999077, China
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Catalysis
  Physical Chemistry
  Inorganic Chemistry
  
• 出版者：Springer Netherlands
• ISSN：1568-5675

文摘

Tumor growth is usually associated with persistent pain, especially during mid and terminal stages of cancer development. Nonetheless, a medicinal compound that possesses both anticancer and analgesic properties has not been identified. The 2-alkylthio-benzofuro[3,2-d]pyrimidin-4(3H)-ones (Code 5a–d) and 1-aryl-2-alkylthio-benzofuro[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-ones (Code 10a–g) were synthesized by using the bioisostere concept, which were obtained via the aza-Wittig reaction of functionalized iminophosphoranes reacted with carbon disulfide and further reaction of the product with alkyl halides or halogenated aliphatic esters. The analgesic properties of 5a–d and 10a–g were studied using rat chronic constriction injury model and the antitumor properties of these chemicals were assessed using MTS cell proliferation assay. Results showed that 5a–d and 10a–g were found to attenuate thermal and mechanical allodynia induced by neuropathy and inhibited the proliferation of three human cancer cell lines (A459, HepG2, and HeLa). Among these compounds, 10g showed highly positive effects in both assessments, and would be selected for future work.