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txy5207铁杆木虫 (正式写手)
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[求助]
求英文翻译一段（药物）
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Following selective secondary binding evaluation for κ opioid and sigma binding, we noted that many compounds of this chemotype possessed potent sigma 1 receptor binding. Although full panel GPCR screening was not completed for this chemotype,six compounds (entries 1–3, 5, 6, and 14 in Table 1) were found to lack submicromolar binding against 5HT6 and D4 (arbitrarily chosen as representative countertargets). Five individual examples of compounds with a single digit nanomolar sigma 1 Kivalue were found (entries 2, 3, 7, 15, and 20). In particular, entry 20 was an exciting result, due to both potency (2 nM Ki) and selectivity (sigma 1:sigma 2:KOR binding ratio of 1∶88∶558). Also of note was that the stereochemistry of the ethyl side chain has little effect on this potent sigma binding because derivatives of both epimers were similarly tight-binding. The sigma 1 secondary binding curves for the compounds in entries 19, 20, and the control compound, haloperidol, are shown in Fig. 5. The binding curves illustrate the dramatic link between activity and basic nitrogen incorporation with compound 10{20}, found to be of comparable potency to haloperidol, and compound 10{19},found to be inactive. An analogous trend was observed for the sigma 2 binding between these compounds, although with a less drastic dependence on basic nitrogen incorporation. Although the structures of 10{20} and haloperidol differ substantially in connectivity, both contain a phenyl group tethered to the basic nitrogen. To assess whether the tricyclic scaffold is contributing significantly to the observed binding activity, the alkyl chain analogue was synthesized (entry 22). Gratifyingly, this analogue retained marked sigma binding affinity, thus dispelling any speculation that an aromatic moiety tethered amine is responsible for the activity. [ Last edited by txy5207 on 2011-7-20 at 20:40 ] |
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【答案】应助回帖
★ ★
sltmac(金币+2): 感谢应助,欢迎常来. 2011-07-21 13:11:58
txy5207(金币+50, 翻译EPI+1): 谢谢了 2011-07-21 20:21:30
sltmac(金币+2): 感谢应助,欢迎常来. 2011-07-21 13:11:58
txy5207(金币+50, 翻译EPI+1): 谢谢了 2011-07-21 20:21:30
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Following selective secondary binding evaluation for κ opioid and sigma binding, we noted that many compounds of this chemotype possessed potent sigma 1 receptor binding. 经过对κ阿片和 sigma受体的选择性次级亲和性评价，我们注意到此系列的许多化合物具有 强的sigma受体亲和力。Although full panel GPCR screening was not completed for this chemotype,six compounds (entries 1–3, 5, 6, and 14 in Table 1) were found to lack submicromolar binding against 5HT6 and D4 (arbitrarily chosen as representative countertargets). 尽管对此系列化合物针对全部GPCR的筛选尚未完结，但可以看到有6种化合物缺乏针对5HT6 和 D4受体的微摩尔以下水平的亲和。Five individual examples of compounds with a single digit nanomolar sigma 1 Ki value were found (entries 2, 3, 7, 15, and 20). 5个化合物的个体例子被发现具有一位数纳摩尔sigma1 Ki值。In particular, entry 20 was an exciting result, due to both potency (2 nM Ki) and selectivity (sigma 1:sigma 2:KOR binding ratio of 1∶88∶558).特别地，化合物20在效能和选择性上都令人鼓舞。 Also of note was that the stereochemistry of the ethyl side chain has little effect on this potent sigma binding because derivatives of both epimers were similarly tight-binding. 同样值得注意的是，两种差向异构体都与受体紧密结合，说明乙基侧链的立体化学对这种对sigma受体的高亲和力贡献不大。The sigma 1 secondary binding curves for the compounds in entries 19, 20, and the control compound, haloperidol, are shown in Fig. 5. 化合物19、20和质控化合物氟哌啶醇的sigma次级亲和力曲线见图5.The binding curves illustrate the dramatic link between activity and basic nitrogen incorporation with compound 10{20}, found to be of comparable potency to haloperidol, and compound 10{19},found to be inactive.亲和力曲线标明，结构中碱性氮和活性之间具有显著联系，化合物10{20}具有与氟哌啶醇相当的效能，而化合物10{19}几无活性。An analogous trend was observed for the sigma 2 binding between these compounds, although with a less drastic dependence on basic nitrogen incorporation. 尽管只具有不那么显著的对碱性氮的依赖，类似的趋势仍可见于类似物对sigma2的亲和性。Although the structures of 10{20} and haloperidol differ substantially in connectivity, both contain a phenyl group tethered to the basic nitrogen. 尽管化合物10{20}与氟哌啶醇在结构连接上大不相同，但它们都含有与碱性氮相连的苯基。To assess whether the tricyclic scaffold is contributing significantly to the observed binding activity, the alkyl chain analogue was synthesized (entry 22). 为了评估三环支架是否与观察到的结合活性显著相关，合成了烷基侧链类似物22.Gratifyingly, this analogue retained marked sigma binding affinity, thus dispelling any speculation that an aromatic moiety tethered amine is responsible for the activity.可喜的是，此类似物保留了显著的sigma亲和性，因而消除了活性源自芳香胺结构的推测。 太长了！！！！！！！！！！！！ 应该100bb以上啊 |
2楼2011-07-21 09:20:25
