(2S)-1-咪唑-1-基-2-(6-甲氧基萘-2-基)丙烷-1-酮 | 917950-84-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: (2S)-1-咪唑-1-基-2-(6-甲氧基萘-2-基)丙烷-1-酮
• 英文名称: 1-(1H-imidazol-1-yl)-2-(2-methoxynaphthalen-6-yl)propan-1-one
• 英文别名: (S)-N-2-naproxenylimidazole；1-imidazole-1-yl-2-(6-methoxy-naphthalen-2-yl)-propan-1-one；(2S)-1-(1H-Imidazol-1-yl)-2-(6-methoxynaphthalen-2-yl)propan-1-one；(2S)-1-imidazol-1-yl-2-(6-methoxynaphthalen-2-yl)propan-1-one
• CAS: 917950-84-6
• 化学式: C₁₇H₁₆N₂O₂
• 分子量: 280.326
• InChiKey: ZRCZMABYWVGAND-LBPRGKRZSA-N

物化性质

• 沸点：
  486.8±47.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-1-咪唑-1-基-2-(6-甲氧基萘-2-基)丙烷-1-酮 在 一水合肼 作用下， 反应 0.03h， 生成 (S)-2-(6-methoxy-2-naphthyl)propanoic acid hydrazide
  参考文献：
  名称：

  Khan, Khalid Mohammed; Salar, Uzma; Fakhri, Muhammad Imran, Letters in Organic Chemistry, 2015, vol. 12, # 9, p. 637 - 644

  摘要：

  DOI：
• 作为产物：
  描述：

  萘普生 在 氯化亚砜 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 苯 为溶剂， 反应 2.0h， 生成 (2S)-1-咪唑-1-基-2-(6-甲氧基萘-2-基)丙烷-1-酮
  参考文献：
  名称：

  Computer Aided Discovery of Potential Anti-inflammatory (S)-naproxen Analogs as COX-2 Inhibitors

  摘要：

  一系列取代的2-(6-甲氧基萘-2-基)丙酸（萘普生）类似物被合成。(S)-萘普生（1）与亚硫酰氯反应生成酰氯（2），随后与不同的杂环基团和芳酸反应，产生了(S)-萘普生类似物（3a-k）。所有化合物都在大鼠足跖水肿模型中进行了抗炎活性筛选，其中大部分活性化合物还研究了其致溃疡潜能。通过分子建模和对接的计算研究，利用Maestro（版本9.1，Schrodinger, LLC.）软件，识别了标题化合物与环氧合酶同工酶（COX-1和COX-2）的假设结合模式。2-(1-(2-(6-甲氧基萘-2-基)丙酰基)-1H-吲哚-2-基)乙酸（3k）在系列中显示为活性最强的化合物，其抑制足跖水肿体积达62.1%，计算结合位点得分为-0.40kcal/mol，致溃疡指数最低为1.19。

  DOI：

  10.2174/1573406411309040009

文献信息

• (<i>R</i>,<i>S</i>)-Azolides as Novel Substrates for Lipase-Catalyzed Hydrolytic Resolution in Organic Solvents
  作者：Pei-Yun Wang、Ying-Ju Chen、An-Chi Wu、Yi-Sheng Lin、Min-Fang Kao、Jin-Ru Chen、Jyun-Fen Ciou、Shau-Wei Tsai

  DOI：10.1002/adsc.200900391

  日期：2009.10

  property and lipase resolution ability in the development of a new resolution process for preparing optically pure carboxylic acids. With the Candida antarctica lipase B (CALB)-catalyzed hydrolysis of (R,S)-N-profenylazoles in organic solvents as the model system, (R,S)-N-profenyl-1,2,4-triazoles instead of their corresponding ester analogues were exploited as the best substrates for preparing optically

  偶氮化合物，即N-酰基唑，作为通用的酰化试剂已在文献中充分表征，其中唑结构不仅可以充当更好的离去基团，还可以使羰基碳更具亲电性，并易于发生亲核攻击。因此，期望在开发用于制备光学纯的羧酸的新的拆分方法的开发中结合这种独特的性质和脂肪酶的拆分能力。以南极假丝酵母脂肪酶B（CALB）-在有机溶剂中催化（R，S）-N-丙烯烯基唑的水解为模型系统，（R，S）-N-profenyl-1,2,4-三唑代替其相应的酯类似物被用作制备光学纯的profen（即2-芳基丙酸）的最佳底物。在45°C下水饱和的甲基叔丁基醚（MTBE）中的（R，S）-偶氮内酯的结构反应性相关性以及彻底的动力学分析进一步用于阐明四面体加合物的限速形成在酰化步骤中，没有CN键断裂或具有适度的CN键断裂与CO键形成协同作用。容易制备底物，高酶反应性和对映体选择性以及通过水萃取容易回收产物和残留底物的优势证明了使用（R，S）-偶氮内酯作为酶促拆分过程的新型底物。
• Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides
  作者：An-Chi Wu、Pei-Yun Wang、Yi-Sheng Lin、Min-Fang Kao、Jin-Ru Chen、Jyun-Fen Ciou、Shau-Wei Tsai

  DOI：10.1016/j.molcatb.2009.11.001

  日期：2010.3

  With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45 degrees C) as the model system, the enzyme enantioselectivity in terms of V-R/V-S = 105.8 and specific activity for the fast-reacting (R)-azolide V-R/(E-t) = 0.979 mmol/(h g) were greatly improved in comparison with V-R/V-S = 8.0 and V-R/(E-t) = 0.113 mmol/(h g) of using (R,S)-naproxenyl 2,2,2-trifluoroethyl ester as the substrate. The resolution strategy was successfully extended to other (R,S)-profenyl 1,2,4-triazolides and lipases from Candida rugosa (Lipase MY) and Carica papaya (CPL) having opposite enantioselectivity to CALB. Moreover, the kinetic constants were estimated, compared with those obtained via hydrolysis, and employed for modeling time-course conversions of (R,S)-naproxenyl 1,2,4-triazolide in anhydrous MTBE. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, as well as easy product separation from the remaining substrate via reactive extraction demonstrate merits of using (R,S)-azolides but not the corresponding esters for the alcoholytic resolution. (C) 2009 Elsevier B.V. All rights reserved.
• WO2006/138187
  申请人：——

  公开号：——

  公开（公告）日：——
• Chondroitin sulfate-based anti-inflammatory macromolecular prodrugs
  作者：Yu-Shiang Peng、Shih-Chun Lin、Shih-Jer Huang、Yu-Ming Wang、Ying-Jer Lin、Li-Fang Wang、Jenn-Shing Chen

  DOI：10.1016/j.ejps.2006.05.010

  日期：2006.9

  Macromolecular prodrugs of three non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen, ketoprofen, and naproxen, were prepared by the covalent attachment of the drugs onto chondroitin sulfate (ChS) using PEG 1000 as a spacer. Drug-PEG adducts were synthesized using 1,1'-carbonyl diimidazole as a coupling agent in dimethyl sulfoxide, followed by the reaction with ChS in highly dilute aqueous solution at pH 6.8 via N-(3-dimethylaminopropyl)N'-ethylcarbodiimide hydrochloride (EDAC) as a conjugation agent. The drug-ChS con confirmed by FTIR, H-1 NMR and C-13 NMR and the molar percent of drug substitution onto ChS was characterized by H-1 NMR using the peak areas of the three protons of -phi CHCH3 on the drugs to those of -NHCOCH3 on ChS. All drug-ChS conjugates are water-soluble. The release amounts of the free drugs from their corresponding drug-ChS conjugates were evaluated in the presence or absence of either esterase or chondroitinase, and the both enzymes in pH 7.4 Tris-buffer solutions at 37 degrees C by high performance liquid chromatography (HPLC). Keto-ChS conjugates. released similar to 100% ketoprofen within 12h in the presence of esterase, but the combination with chondroitinase did not accelerate the release rate. The degradation of Keto-ChS conjugates by chondroitinase was confirmed by gel permeation chromatography (GPC). The Keto-ChS conjugates still retained the enzymatic recognition even at the substitution of ketoprofen as high as 56 mol%. The inhibition percent of carrageenan-induced edema of Keto-ChS-56 was comparable to that of a simple blend of ChS and ketoprofen, suggesting that biologically active ChS and ketoprofen could be liberated from the conjugate. (c) 2006 Elsevier B.V.All rights reserved.