Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy
文献类型：期刊论文
| 作者 | Sun, Hao1; Shi, Min1; Zhang, Wei1; Zheng, Yue-Ming2; Xu, Ya-Zhou3; Shi, Jun-Jie1; Liu, Ting1; Gunosewoyo, Hendra4; Pang, Tao3; Gao, Zhao-Bing2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2016-07-14 |
| 卷号 | 59期号:13页码:6329-6343 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.6b00571 |
| 文献子类 | Article |
| 英文摘要 | A novel series of sigma (sigma) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (K-i < 1 nM) and selective sigma 1 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 sigma 1 ligands for antinociception is warranted. This study supports the notion that selective sigma 1 antagonism could be a useful strategy in the development of novel antipain therapy. |
| WOS关键词 | BLOOD-BRAIN-BARRIER ; BIOLOGICAL EVALUATION ; FORMALIN TEST ; PAIN ; LIGANDS ; IDENTIFICATION ; ENHANCEMENT ; SCAFFOLD ; AGONIST ; SERIES |
| 资助项目 | National Natural Science Foundation of China[81402780] ; Natural Science Foundation of Shanghai[14ZR1411000] ; Innovation Program of East China Normal University[78210263] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000379989800026 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275959]  |
| 专题 | 神经药理学研究国际科学家工作站 |
| 通讯作者 | Tang, Jie; Yu, Li-Fang |
| 作者单位 | 1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 501 Hai Ke Rd, Shanghai 201203, Peoples R China; 3.China Pharmaceut Univ, State Key Lab Nat Med, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China; 4.Curtin Univ, Fac Hlth Sci, Sch Pharm, Perth, WA 6102, Australia; 5.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Hao,Shi, Min,Zhang, Wei,et al. Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(13):6329-6343. |
| APA | Sun, Hao.,Shi, Min.,Zhang, Wei.,Zheng, Yue-Ming.,Xu, Ya-Zhou.,...&Yu, Li-Fang.(2016).Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy.JOURNAL OF MEDICINAL CHEMISTRY,59(13),6329-6343. |
| MLA | Sun, Hao,et al."Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy".JOURNAL OF MEDICINAL CHEMISTRY 59.13(2016):6329-6343. |
入库方式： OAI收割
来源：上海药物研究所
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