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Synthesis, biological activities, and 3D-QSAR studies of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety

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Abstract

To discover a novel lead structure for antiphytopathogenic fungus agent, a series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety were designed and synthesized. They were determined by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). The biological activity results revealed that these title compounds possessed antifungal and insecticidal activities. Some title compounds against Alternaria solani, Physalospora piricola, Cercospora arachidicola, Phytophthora capsici, Fusarium graminearum, and Sclerotinia sclerotiorum displayed moderate to good antifungal activities at 50 mg/L, especially, compounds 6b and 6p displayed good and broad-spectrum antifungal activities. The structure activity relationships were discussed. A 3D-QSAR model was established based on the antifungal activity against Phytophthora capsici, indicating that electrostatic and hydrophobic fields were the two most significant factors for antifungal activity. Hence, structure optimization based on the CoMSIA model was performed to find compound 6p with excellent activity against Phytophthora capsici, and the EC50 values of compound 6p were comparable to those of chlorothalonil. Furthermore, the insecticidal activity of compound 6p against Culex pipiens larvae at 1 mg/L was considerable to that of chlorantraniliprole. Therefore, compound 6p can be used as a novel lead structure for antiphytopathogenic fungus and insecticidal agent development.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (nos. 31901908 and 31972287), the Natural Science Foundation of Tianjin (no. 19JCQNJC04600), the Scientific Project of Tianjin Municipal Education Commission (no. 2018KJ008), the National Student’s Platform for Innovation and Entrepreneurship Training Program (no. 201810061003).

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Correspondence to Jingbo Liu or Yuxin Li.

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Liu, J., Li, F., Wang, Y. et al. Synthesis, biological activities, and 3D-QSAR studies of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety. Med Chem Res (2020) doi:10.1007/s00044-020-02499-3

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Keywords

  • (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide
  • Sulfonohydrazide
  • Antifungal activity
  • Insecticidal activity
  • Structure activity relationship