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411iloveyo木蟲 (小有名氣)
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求高手翻譯兩段 英譯漢
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Three potent Sig-R binding compounds—10{20}, 10{22}, and 10{7} (which contains two basic nitrogen atoms)—were evaluated for their GPCR selectivity against 38 targets, and the results were incorporated in Table 1 (see SI Appendix for a heat map– formatted selectivity table). The three compounds displayed >86∶1 selectivities for the limited number of receptors for which binding was observed at all; an impressive result for compounds obtained in such an abbreviated structure-activity optimization exercise. The N-propyl derivative 10{22}, designed to eliminate binding arising from a pendant aryl-containing side chain, was particularly selective. Here, the only non-Sig-R binding was detected against the 5HT1A receptor (Ki ¼ 4;500 nM) as opposed to Sig-R 1 and Sig-R 2 (Ki values of 12 and 288 nM, respectively), As part of our efforts toward greater skeletal diversity, additional ring systems were introduced through modifications of the ketone carbonyl on scaffolds constructed by a Diels–Alder/ Schmidt reaction sequence.We applied the isocyanide multicomponent reaction (MCR) methodology developed by Shaabani et al. to transform the ketone carbonyl to the spirocyclic nitrogen heterocycles shown (Scheme 4) (45). This protocol smoothly incorporated three elements of diversity in a single operation to afford 44 heterocyclic analogues synthesized from the fragment pool in Scheme 4. This chemotype possesses an intriguing, complex spirocyclic molecular architecture not reported from any natural sources and incorporating three additional basic nitrogen sites. Although the MCR was not completely diastereoselective, a trend we had previously observed in the reductive amination at the same ketone carbonyl (39), the reaction did afford a dominant diastereomer that was assigned based on the X-ray crystal structure of the isolated compound 14{44}. Screening the full compound set for κ opioid, sigma 1, and sigma 2 receptor binding (Ki values) revealed a number of compounds with modest binding for these targets. Thus, compound 14{11} emerged as the most potent Sig-R binding candidate (Ki ¼ 867, 280 nM for sigma 1 and sigma 2, respectively) and compound 14{15} was found to possess the most potent κ opioid binding (Ki ¼ 407 nM) along with modest sigma 1 binding (Ki ¼ 1;158 nM). Sixteen of the 44 compounds were also evaluated for 5HT1A binding, with only compound 14{26} found to possess significant 5HT1A binding activity (Ki ¼ 431 nM). In addition, four compounds were screened against the full 43 GPCR assay panel as described previously for neostenine. The results showed this compound subset to be free from promiscuous binding, and compound 14{41} was discovered to possess selective adrenergic binding affinity (Ki ¼ 1;156, 7,588 nM for Alpha1A and Alpha1B, respectively). Representative structures of this chemotype and associated binding activity are shown in Scheme 4 (for complete data on all compounds, see SI Appendix). |
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8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
2樓2011-07-22 08:40:34
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
★ ★
sltmac(金幣+2): 感謝應(yīng)助~ 2011-07-22 16:06:21
sltmac(金幣+2): 感謝應(yīng)助~ 2011-07-22 16:06:21
| Three potent Sig-R binding compounds—10{20}, 10{22}, and 10{7} (which contains two basic nitrogen atoms)—were evaluated for their GPCR selectivity against 38 targets, and the results were incorporated in Table 1 (see SI Appendix for a heat map– formatted selectivity table). 評估了三種具有強(qiáng)Sig-R親和性、結(jié)構(gòu)中含有兩個堿性氮原子的化合物10{20}, 10{22}和 10{7} 對38種靶標(biāo)的GPCR選擇性，結(jié)果總結(jié)在表1中。The three compounds displayed >86∶1 selectivities for the limited number of receptors for which binding was observed at all; an impressive result for compounds obtained in such an abbreviated structure-activity optimization exercise.在全部考察了親和性的受體中，這三種化合物對有限數(shù)量的受體顯示了>86∶1的選擇性；對于通過簡單構(gòu)效優(yōu)化獲得的化合物而言，這是一個給人印象深刻的結(jié)果。The N-propyl derivative 10{22}, designed to eliminate binding arising from a pendant aryl-containing side chain, was particularly selective. 被設(shè)計以消除由于含芳基側(cè)鏈而引起的親和性的 N-丙基衍生物10{20} 表現(xiàn)了突出的選擇性。Here, the only non-Sig-R binding was detected against the 5HT1A receptor (Ki ¼ 4;500 nM) as opposed to Sig-R 1 and Sig-R 2 (Ki values of 12 and 288 nM, respectively), 這里，檢測到的唯一的非-Sig-R親和性是針對與Sig-R 1和2截然相反的5HT1A。 |
3樓2011-07-22 09:09:02
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
| As part of our efforts toward greater skeletal diversity, additional ring systems were introduced through modifications of the ketone carbonyl on scaffolds constructed by a Diels–Alder/ Schmidt reaction sequence.作為我們增加骨架多樣性工作的一部分，通過Diels–Alder/ Schmidt 序列反應(yīng)對酮羰基加以修飾引入額外的環(huán)系統(tǒng)。We applied the isocyanide multicomponent reaction (MCR) methodology developed by Shaabani et al. to transform the ketone carbonyl to the spirocyclic nitrogen heterocycles shown (Scheme 4) (45). 采用由Shaabani 等開發(fā)的MCR方法，我們將酮羰基化合物轉(zhuǎn)化為螺環(huán)型氮雜環(huán)化合物，見示意圖4. This protocol smoothly incorporated three elements of diversity in a single operation to afford 44 heterocyclic analogues synthesized from the fragment pool in Scheme 4. 通過恰當(dāng)?shù)膶⒍鄻有运璧娜齻�成分整合到一步操作中，實現(xiàn)通過示意圖4中所示程序合成44中雜環(huán)類似物的目的。This chemotype possesses an intriguing, complex spirocyclic molecular architecture not reported from any natural sources and incorporating three additional basic nitrogen sites. 此化學(xué)型具有有趣的尚未見源自天然產(chǎn)物有關(guān)報道的復(fù)雜螺環(huán)分子結(jié)構(gòu)， 含有三個額外的堿性氮點位。 |
4樓2011-07-22 09:31:08
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
| Although the MCR was not completely diastereoselective, a trend we had previously observed in the reductive amination at the same ketone carbonyl (39), the reaction did afford a dominant diastereomer that was assigned based on the X-ray crystal structure of the isolated compound 14{44}. 盡管我們先前在相同酮羰基化合物的還原性胺化中觀察到MCR反應(yīng)不是完全非對映選擇性的，這里的反應(yīng)確實產(chǎn)生了一個主導(dǎo)性的對映異構(gòu)體（由分離化合物的X射線衍射晶體結(jié)構(gòu)確定）。Screening the full compound set for κ opioid, sigma 1, and sigma 2 receptor binding (Ki values) revealed a number of compounds with modest binding for these targets. 對全部化合物系列進(jìn)行的針對k阿片、sigma1和sigma2 受體親和性的篩選顯示了若干對這些受體具有適度親和性的化合物。 |
5樓2011-07-22 09:47:01
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
6樓2011-07-22 09:47:31
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
★
Mally89(金幣+1): 再加一個！~專家辛苦了！~ 2011-07-23 21:22:05
411iloveyo(金幣+300, 翻譯EPI+1): 西西 謝謝。。。。。 2011-07-25 08:15:46
Mally89(金幣+1): 再加一個！~專家辛苦了！~ 2011-07-23 21:22:05
411iloveyo(金幣+300, 翻譯EPI+1): 西西 謝謝。。。。。 2011-07-25 08:15:46
| Thus, compound 14{11} emerged as the most potent Sig-R binding candidate (Ki ¼ 867, 280 nM for sigma 1 and sigma 2, respectively) and compound 14{15} was found to possess the most potent κ opioid binding (Ki ¼ 407 nM) along with modest sigma 1 binding (Ki ¼ 1;158 nM). 由此發(fā)現(xiàn)作為最強(qiáng)Sig-R親和性候選化合物14{11}和化合物14{15}具有最強(qiáng)的k阿片受體親和性和中度的sigma 1受體親和性。Sixteen of the 44 compounds were also evaluated for 5HT1A binding, with only compound 14{26} found to possess significant 5HT1A binding activity (Ki ¼ 431 nM).還評估了44種化合物中的16種對5HT1A受體的親和性，發(fā)現(xiàn)只有化合物14{26}具有顯著的5HT1A結(jié)合活性。 In addition, four compounds were screened against the full 43 GPCR assay panel as described previously for neostenine. 此外，還對4種化合物進(jìn)行了如前所述對新斯替寧堿所進(jìn)行的針對43種GPCR的組合篩選。The results showed this compound subset to be free from promiscuous binding, and compound 14{41} was discovered to possess selective adrenergic binding affinity (Ki ¼ 1;156, 7,588 nM for Alpha1A and Alpha1B, respectively). 結(jié)果顯示這幾個化合物缺乏各式各樣的親和性，化合物14{41}具有選擇性腎上腺素能受體親和性。Representative structures of this chemotype and associated binding activity are shown in Scheme 4 (for complete data on all compounds, see SI Appendix).此化學(xué)型種典型的結(jié)構(gòu)及與之相聯(lián)系的結(jié)合活性情況見示意圖4.（所有化合物的完備資料，見附錄SI。） |
7樓2011-07-23 08:19:16
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