Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis
Selective CB 2 agonists represent an attractive therapeutic strategy for the treatment of a variety of diseases without psychiatric side effects mediated by the CB 1 receptor. We carried out a rational optimization of a black market designer drug SDB-001 that led to the identification of potent an...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
American Chemical Society
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/56683 |
| _version_ | 1848759913534193664 |
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| author | Shi, Y. Duan, Y. Ji, Y. Wang, Z. Wu, Y. Gunosewoyo, Hendra Xie, X. Chen, J. Yang, F. Li, J. Tang, J. Xie, X. Yu, L. |
| author_facet | Shi, Y. Duan, Y. Ji, Y. Wang, Z. Wu, Y. Gunosewoyo, Hendra Xie, X. Chen, J. Yang, F. Li, J. Tang, J. Xie, X. Yu, L. |
| author_sort | Shi, Y. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Selective CB 2 agonists represent an attractive therapeutic strategy for the treatment of a variety of diseases without psychiatric side effects mediated by the CB 1 receptor. We carried out a rational optimization of a black market designer drug SDB-001 that led to the identification of potent and selective CB 2 agonists. A 7-methoxy or 7-methylthio substitution at the 3-amidoalkylindoles resulted in potent CB 2 antagonists (27 or 28, IC 50 = 16-28 nM). Replacement of the amidoalkyls from 3-position to the 2-position of the indole ring dramatically increased the agonist selectivity on the CB 2 over CB 1 receptor. Particularly, compound 57 displayed a potent agonist activity on the CB 2 receptor (EC 50 = 114-142 nM) without observable agonist or antagonist activity on the CB 1 receptor. Furthermore, 57 significantly alleviated the clinical symptoms and protected the murine central nervous system from immune damage in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. |
| first_indexed | 2025-11-14T10:07:26Z |
| format | Journal Article |
| id | curtin-20.500.11937-56683 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:07:26Z |
| publishDate | 2017 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-566832018-02-06T03:28:46Z Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis Shi, Y. Duan, Y. Ji, Y. Wang, Z. Wu, Y. Gunosewoyo, Hendra Xie, X. Chen, J. Yang, F. Li, J. Tang, J. Xie, X. Yu, L. Selective CB 2 agonists represent an attractive therapeutic strategy for the treatment of a variety of diseases without psychiatric side effects mediated by the CB 1 receptor. We carried out a rational optimization of a black market designer drug SDB-001 that led to the identification of potent and selective CB 2 agonists. A 7-methoxy or 7-methylthio substitution at the 3-amidoalkylindoles resulted in potent CB 2 antagonists (27 or 28, IC 50 = 16-28 nM). Replacement of the amidoalkyls from 3-position to the 2-position of the indole ring dramatically increased the agonist selectivity on the CB 2 over CB 1 receptor. Particularly, compound 57 displayed a potent agonist activity on the CB 2 receptor (EC 50 = 114-142 nM) without observable agonist or antagonist activity on the CB 1 receptor. Furthermore, 57 significantly alleviated the clinical symptoms and protected the murine central nervous system from immune damage in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. 2017 Journal Article http://hdl.handle.net/20.500.11937/56683 10.1021/acs.jmedchem.7b00724 American Chemical Society restricted |
| spellingShingle | Shi, Y. Duan, Y. Ji, Y. Wang, Z. Wu, Y. Gunosewoyo, Hendra Xie, X. Chen, J. Yang, F. Li, J. Tang, J. Xie, X. Yu, L. Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis |
| title | Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis |
| title_full | Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis |
| title_fullStr | Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis |
| title_full_unstemmed | Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis |
| title_short | Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis |
| title_sort | amidoalkylindoles as potent and selective cannabinoid type 2 receptor agonists with in vivo efficacy in a mouse model of multiple sclerosis |
| url | http://hdl.handle.net/20.500.11937/56683 |