Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy
A novel series of sigma (s) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki < 1 nM) and selective s1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
American Chemical Society
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/18018 |
| _version_ | 1848749624846712832 |
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| author | Sun, H. Shi, M. Zhang, W. Zheng, Y. Xu, Y. Shi, J. Liu, T. Gunosewoyo, Hendra Pang, T. Gao, Z. Yang, F. Tang, J. Yu, L. |
| author_facet | Sun, H. Shi, M. Zhang, W. Zheng, Y. Xu, Y. Shi, J. Liu, T. Gunosewoyo, Hendra Pang, T. Gao, Z. Yang, F. Tang, J. Yu, L. |
| author_sort | Sun, H. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | A novel series of sigma (s) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki < 1 nM) and selective s1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT. In particular, compound 53 was shown to possess significant antinociceptive activity in the mouse formalin-induced inflammation pain model when administered intraperitoneally at 40 and 80 mg/kg. Initial pharmacokinetics evaluation indicated an excellent brain exposure following oral dosing in mice, suggesting that further investigation into the use of alkoxyisoxazoles as s1 ligands for antinociception is warranted. This study supports the notion that selective s1 antagonism could be a useful strategy in the development of novel antipain therapy. |
| first_indexed | 2025-11-14T07:23:54Z |
| format | Journal Article |
| id | curtin-20.500.11937-18018 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:23:54Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-180182017-09-13T15:44:54Z Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy Sun, H. Shi, M. Zhang, W. Zheng, Y. Xu, Y. Shi, J. Liu, T. Gunosewoyo, Hendra Pang, T. Gao, Z. Yang, F. Tang, J. Yu, L. A novel series of sigma (s) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki < 1 nM) and selective s1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT. In particular, compound 53 was shown to possess significant antinociceptive activity in the mouse formalin-induced inflammation pain model when administered intraperitoneally at 40 and 80 mg/kg. Initial pharmacokinetics evaluation indicated an excellent brain exposure following oral dosing in mice, suggesting that further investigation into the use of alkoxyisoxazoles as s1 ligands for antinociception is warranted. This study supports the notion that selective s1 antagonism could be a useful strategy in the development of novel antipain therapy. 2016 Journal Article http://hdl.handle.net/20.500.11937/18018 10.1021/acs.jmedchem.6b00571 American Chemical Society restricted |
| spellingShingle | Sun, H. Shi, M. Zhang, W. Zheng, Y. Xu, Y. Shi, J. Liu, T. Gunosewoyo, Hendra Pang, T. Gao, Z. Yang, F. Tang, J. Yu, L. Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy |
| title | Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy |
| title_full | Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy |
| title_fullStr | Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy |
| title_full_unstemmed | Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy |
| title_short | Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy |
| title_sort | development of novel alkoxyisoxazoles as sigma-1 receptor antagonists with antinociceptive efficacy |
| url | http://hdl.handle.net/20.500.11937/18018 |