Benzylpiperidine derivatives as new dual μ-opioid and σ 1 receptor ligands with potent antinociceptive effects
Bioorganic Chemistry, ISSN: 0045-2068, Vol: 153, Page: 107921
2024
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Article Description
Dual-acting μ-opioid receptor (MOR)/sigma-1 receptor (σ 1 R) ligands have displayed promise in exerting robust antinociceptive effects while reducing opioid-related side effects. To discover safer and more effective analgesics, we designed, prepared, and evaluated 30 benzylpiperidine derivatives as dual MOR and σ 1 R ligands. The obtained benzylpiperidine analogs were tested for MOR and σ 1 R binding affinity in vitro. The best compound 52 showed high affinity for both MOR [ K i (MOR) = 56.4 nM] and σ 1 R [ Ki (σ 1 R) = 11.0 nM] and produced potent antinociceptive effects in the abdominal contraction test (ED 50 = 4.04 mg/kg in mice), carrageenan-induced inflammatory pain model (ED 50 = 6.88 mg/kg in mice), formalin test (ED 50 = 13.98 mg/kg in rats) and complete Freund’s adjuvant (CFA)-induced chronic pain model (ED 50 = 7.62 mg/kg in mice). Moreover, 52 had less MOR-related adverse effects than oxycodone, including constipation, acute hyperlocomotion and physical dependence. The above results suggested that 52 may be a promising candidate for the development of safer analgesics.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0045206824008265; http://dx.doi.org/10.1016/j.bioorg.2024.107921; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85207951329&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/39492131; https://linkinghub.elsevier.com/retrieve/pii/S0045206824008265
Elsevier BV
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know