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

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Abstract

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.

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Acknowledgments

We gratefully acknowledge financial support of this work by the National Natural Science Foundation of Hubei Provincial (No.2011CDC006) and the fund of Hubei 2011 Cooperative Innovation Center (No. 2011JH-2014CXTT07), Key Project of Project of Hubei University of Medicine (No. 2014XKJSXJ06, 2014XKJSSJ04, 2011CXX03 and 2014CXZ-05) and Natural Science Foundation of Hubei Province of China (No. 2012FFC060); Natural Science Foundation of Hubei University of Medicine (No. 2011QDZR-2).

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Authors and Affiliations

  1. Department of Anesthesiology, Institute of Anesthesiology, Taihe Hospital of Hubei University of Medicine, Shiyan, 442000, China

    Qing Li & Yang-Gen Hu

  2. Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry, Hubei University of Medicine, Shiyan, 442000, China

    Qing Li & Yang-Gen Hu

  3. Department of Medical Laboratory Science, Taihe Hospital of Hubei University of Medicine, Shiyan, 442000, China

    Yong-Mei Chen

  4. Department of Anaesthesiology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China

    Xin Luo & Chi Wai Cheung

  5. Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 999077, China

    Joshua Ka Shun Ko

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  1. Qing Li
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  2. Yong-Mei Chen
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  3. Yang-Gen Hu
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Correspondence to Yang-Gen Hu.

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Li, Q., Chen, YM., Hu, YG. et al. Synthesis and biological activity of fused furo[2,3-d]pyrimidinone derivatives as analgesic and antitumor agents. Res Chem Intermed 42, 939–949 (2016). https://doi.org/10.1007/s11164-015-2064-8

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  • DOI: https://doi.org/10.1007/s11164-015-2064-8

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