Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1374–1383 | Cite as

Synthesis, crystal structure, and antinociceptive effects of some new riluzole derivatives

Original Research
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Abstract

Nine N-alkylated derivatives of riluzole were synthesized in order to obtain new compounds with potential antinociceptive activity. Riluzole was firstly transformed into (6-trifluoromethoxy-benzothiazol-2-yl)-hydrazine, then it was chlorinated by SOCl2 to obtain 2-chloro-6-trifluoromethoxy-benzothiazole. This intermediate product was treated with nine alkylamines to give N-alkylated derivatives of riluzole respectively. The structures of compounds were confirmed by means of elemental analysis, IR, 1H NMR, and 13C NMR. The synthetic route was optimized and four novel crystals were obtained by recrystallization. This study investigated the antinociceptive activity of some N-alkylated derivatives of riluzole by hot plate test in mice. The relationship between antinociceptive activity and the doses of 4b, 4c, 4h, 4g, and riluzole had been studied. Compared with the control group (0 mg/kg), the effects of compounds 4b and 4h showed a significant increase (13.78 ± 2.89 s, 12.89 ± 2.94 s, respectively). Compound 4c showed extreme significant increase (18.07 ± 3.08 s) in the time mice spent on the hot plate. The compounds 4b, 4c, and 4h had increased the latency time compared to the blank solvent group. They have potential application in developing new drug candidates with antinociceptive activity.

Keywords

Riluzole Benzothiazole derivatives Antinociceptive Synthesis Crystal structure 

Notes

Acknowledgements

The work was supported by the National Natural Science Foundation of China (No. 21202130), the Fundamental Research Funds for the Central Universities (No. 3102014JCQ15005), the Natural Science Foundation Research Project of Shaanxi Province (No. 2015JM2067), the Seed Foundation of Innovation and Creation for Graduate Students in Northwestern Polytechnical University (No. Z2017239), the national innovation experiment program for university students (No.201610699258)

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2154_MOESM1_ESM.doc (6.9 mb)
Supplementary Information

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory for Space Bioscience and Biotechnology, School of Life SciencesNorthwestern Polytechnical UniversityXi’anChina

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