| Autor: |
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 |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
European journal of medicinal chemistry. 243 |
| ISSN: |
1768-3254 |
| Popis: |
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 (ED |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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Full Text from ScienceDirect