Thiophenpiperazine amide derivatives as new dual MOR and σ 1 R ligands for the treatment of pain.

A new series of thiophenpiperazine amide derivatives as potent dual ligands for the μ-opioid (MOR) and sigma-1 (σ ₁ R) receptors are reported. Compound 23 exhibited good affinity to σ ₁ R (K _i  = 44.7 ± 7.05 nM) and high selectivity to σ ₂ R. Furthermore, Compound 23 exerted MOR agonism and σ1R antagonism and potent analgesic activity in animal moldes (the abdominal constriction test (ED ₅₀  = 3.83 mg/kg) and carrageenan-induced inflammatory hyperalgesia model (ED ₅₀  = 5.23 mg/kg)). We obtained new dual ligands that might serve as starting points for preparing targeted tools. Furthermore, 23 may be a useful chemical probe for understanding more fully analgesic effects associated with MOR agonism and σ ₁ R antagonism.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xudong Cao reports financial support was provided by National Natural Science Foundation of China. Xudong Cao reports financial support was provided by Natural Science Foundation of Jiangsu Province. Xudong Cao reports financial support was provided by Natural Science Foundation of the Jiangsu Higher Education Institutions of China. Xudong Cao reports financial support was provided by Science and Technology Project of Xuzhou City. Xudong Cao reports financial support was provided by the Youth Foundation of Xuzhou Medical University. Tao Zhuang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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