Benzo[b]thiophene-2-carboxamides as novel opioid receptor agonists with potent analgesic effect and reduced constipation

Ramajayam Kuppusamy, Ying Ting Hsu, Yi Yu Ke, Po Wei Chang, Yung Chiao Chang, Hsiao Fu Chang, Pei Chen Wang, Yu Hao Lin, Yu Chen Huang, Teng Kuang Yeh, Jian Ying Chuang, Horace H. Loh, Chuan Shih, Chiung Tong Chen, Shiu Hwa Yeh, Shau Hua Ueng

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)


Currently, there is a significant unmet need for novel analgesics with fewer side effects. In this study, we carried out structural modification of a hit compound previously identified in an artificial-intelligence (AI) virtual screening and discovered the potent analgesic, benzo[b]thiophene-2-carboxamide analog (compound 25) with new structural scaffold. We investigated the signaling pathways of opioid receptors mediated by compound 25, and found this racemic compound activated mu-opioid receptor through the cyclic adenosine monophosphate (cAMP) and β-arrestin-2-mediated pathways with strong potency and efficacy, and accompanying nociceptin-orphanin FQ opioid peptide and delta-opioid receptors through the cAMP pathway with weak potencies. Compound 25 elicited potent antinociception in thermal-stimulated pain (ED50 value of 127.1 ± 34.65 μg/kg) and inflammatory-induced allodynia models with less gastrointestinal transit inhibition and antinociceptive tolerance than morphine. Overall, this study revealed a novel analgesic with reduced risks of side effects.
期刊European Journal of Medicinal Chemistry
出版狀態已發佈 - 12月 2022

ASJC Scopus subject areas

  • 藥理
  • 藥物發現
  • 有機化學


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