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Novel norsufentanil analogues containing triazole ring; synthesis, radioligand binding assay, and pharmacological evaluation

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Abstract

A series of 12 novel triazoles containing derivatives of norsufentanil were put into synthesis having the construction of the alkynyl group on norsufentanil followed by copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Every single one of the synthesized compounds was evaluated through radioligand binding experiments. The compounds with the best affinities in the in vitro studies were selected to be investigated for their anti-nociceptive activity by way of tail flick test. Compounds 3h and 3i (Ki = 0.55 nM; IC50 = 1.25 nM and, Ki = 0.83 nM; IC50 = 1.87 nM, respectively) displayed the best affinities compared to that of sufentanil’s (Ki = 0.70 nM; IC50 = 1.59 nM). 3h put on display the highest potency (ED50 = 4.21 µg/kg) for tail flick test amongst the entire selected compounds.

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Acknowledgements

The authors acknowledge partial support of Research and Technology Council of Shahid Beheshti University and Deputy of Research, Shahid Beheshti University of Medical Sciences for grant No. 313/329.

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Authors and Affiliations

  1. Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, 1983963113, Tehran, Iran

    Majid Nami, Peyman Salehi, Morteza Bararjanian, Nazanin Seighal Delshad & Bahareh Heidari

  2. Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, 2660 Vali-e-Asr Ave., 1991953381, Tehran, Iran

    Mona Khoramjouy

  3. Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy and Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, 2660 Vali-e-Asr Ave., 1991953381, Tehran, Iran

    Soraya Shahhosseini

  4. Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 2660 Vali-e-Asr Ave., 1991953381, Tehran, Iran

    Mehrdad Faizi

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  1. Majid Nami
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The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.

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Correspondence to Peyman Salehi.

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Nami, M., Salehi, P., Bararjanian, M. et al. Novel norsufentanil analogues containing triazole ring; synthesis, radioligand binding assay, and pharmacological evaluation. Med Chem Res 31, 886–893 (2022). https://doi.org/10.1007/s00044-022-02874-2

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