酮洛芬乙酯 | 60658-04-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 酮洛芬乙酯
• 英文名称: ketoprofen ethyl ester
• 英文别名: ethyl 2-(3-benzoylphenyl)propanoate
• CAS: 60658-04-0
• 化学式: C₁₈H₁₈O₃
• 分子量: 282.339
• InChiKey: CQSMNXCTDMLMLM-UHFFFAOYSA-N

物化性质

• 沸点：
  402.3±28.0 °C(Predicted)
• 密度：
  1.111±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、乙酸乙酯（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  储存条件：室温、密封、干燥

反应信息

• 作为反应物：
  描述：

  酮洛芬乙酯 在 native lipase from Candida rugosa 、 水 作用下， 生成 右旋酮洛芬
  参考文献：
  名称：

  化学酶法合成纯对映体2-芳基丙酸。

  摘要：

  描述了一种获得纯对映体2-芳基丙酸的新化学酶法。一锅合成（±）-2-芳基丙酸是通过将二氯卡宾加成至芳基甲基酮的O键并加成产物进行氢解来进行的。外消旋混合物通过使用来自假丝酵母的天然脂肪酶的外消旋乙酯的对映体特异性水解来拆分。良好的收率，起始的芳基甲基酮的可及性和酶促水解的立体特异性使该方法变得有趣，以便获得相同的非甾体类抗炎药，如布洛芬或萘普生。

  DOI：

  10.1016/s0040-4020(01)81926-8
• 作为产物：
  描述：

  3-苄基环己烷-1-酮 在 Celite 、 硫酸 、 sodium hydride 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙酸酐 、 溶剂黄146 、 paraffin 、 苯 为溶剂， 反应 20.5h， 生成 酮洛芬乙酯
  参考文献：
  名称：

  Mitra, R. B.; Joshi, Vijaya S., Synthetic Communications, 1988, vol. 18, # 18, p. 2259 - 2266

  摘要：

  DOI：

文献信息

• Aminoazole derivatives and their production and use
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：US04914112A1

  公开（公告）日：1990-04-03

  A compound of the formula: ##STR1## wherein A is the group of the formula: Ar.sup.1 --D--Ar.sup.2 -- wherein Ar.sup.1 is a phenyl or thienyl group which may be optionally substituted with at least one of the same or different halogen atom; Ar.sup.2 is a phenylene or thienylene group which may be optionally substituted with at least one of the same or different halogen atom; D is a divalent radical selected from the group consisting of >C.dbd.N--OR.sup.4 [wherein R.sup.4 is a hydrogen atom or lower alkyl group], >C.dbd.O, ##STR2## >CHOH, >NH radical, or single bond, ##STR3## wherein R.sup.5 is a lower alkoxy or a phenyl group which may be optionally substituted with at least one of the same or different halogen atom; E is a methine group or a nitrogen atom; F is a vinylene group or an oxygen atom, ##STR4## wherein R.sup.6 is a lower alkoxy group; R.sup.7 is a lower alkyl group; R.sup.8 is a benzoyl group which may be optionally substituted with at least one of the same or different halogen atom, B is a divalent azole group; R.sup.1 is a hydrogen atom or a lower alkyl group; R.sup.2 is a hydrogen atom, lower alkyl, aryl-lower alkyl, or the group of the formula: R.sup.9 --G-- wherein R.sup.9 is a hydrogen atom, lower alkyl, halo-lower alkyl, amino-lower alkyl, aryl or aryl-lower alkyl group or the group of the formula: ##STR5## wherein R.sup.10 is a hydrogen atom or lower alkoxy group; R.sup.11 is a hydrogen atom, lower alkyl, lower alkenyl, lower cycloalkyl, aryl-lower alkyl, aryl or aroyl group; or the group of the formula: --NR.sup.10 R.sup.11 is a 5-, 6- or 7-membered saturated heterocyclic ring; or the group of the formula: R.sup.12 --O-- wherein R.sup.12 is a lower alkyl or polyhalo-lower alkyl group; G is a divalent group selected from the group consisting of >C.dbd.O, >C.dbd.S, >(C.dbd.O).sub.2 or >SO.sub.2 radical; or the group of the formula: --NR.sup.1 R.sup.2 is a 5-, 6- or 7-membered saturated heterocyclic ring: R.sup.3 is a hydrogen atom or lower alkyl group, or its acid addition salts, which is useful for immunomodulator.

  该化合物的化学式为：##STR1## 其中A是该式的基团：Ar.sup.1 --D--Ar.sup.2 -- 其中Ar.sup.1是苯基或噻吩基团，可以选择性地用相同或不同的卤原子取代；Ar.sup.2是苯基或噻吩基团，可以选择性地用相同或不同的卤原子取代；D是从以下组中选择的二价基团：>C.dbd.N--OR.sup.4 [其中R.sup.4是氢原子或较低的烷基基团]，>C.dbd.O，##STR2## >CHOH，>NH基团，或单键，##STR3## 其中R.sup.5是较低的烷氧基或苯基团，可以选择性地用相同或不同的卤原子取代；E是亚甲基基团或氮原子；F是乙烯基团或氧原子，##STR4## 其中R.sup.6是较低的烷氧基；R.sup.7是较低的烷基基团；R.sup.8是苯甲酰基团，可以选择性地用相同或不同的卤原子取代，B是二价唑基团；R.sup.1是氢原子或较低的烷基基团；R.sup.2是氢原子，较低的烷基，芳基-较低的烷基，或该式的基团：R.sup.9 --G-- 其中R.sup.9是氢原子，较低的烷基，卤代较低的烷基，氨基-较低的烷基，芳基或芳基-较低的烷基团，或该式的基团：##STR5## 其中R.sup.10是氢原子或较低的烷氧基；R.sup.11是氢原子，较低的烷基，较低的烯基，较低的环烷基，芳基-较低的烷基，芳基或芳酰基团；或该式的基团：--NR.sup.10 R.sup.11是5、6或7-成员饱和杂环；或该式的基团：R.sup.12 --O-- 其中R.sup.12是较低的烷基或多卤代较低的烷基基团；G是从以下组中选择的二价基团：>C.dbd.O，>C.dbd.S，>(C.dbd.O).sub.2或>SO.sub.2基团；或该式的基团：--NR.sup.1 R.sup.2是5、6或7-成员饱和杂环：R.sup.3是氢原子或较低的烷基基团，或其酸盐，用于免疫调节剂。
• Fabrication of organogels achieved by prodrug-based organogelators of ketoprofen
  作者：Rahul R. Mahire、Deepika S. Agrawal、Devanand K. Patil、Dhananjay H. More

  DOI：10.1039/c4ra03688c

  日期：——

  The treatment strategy of curing diseases using prodrugs of an anti-inflammatory drug is widespread. In the present study, we report on the synthesis of prodrugs of ketoprofen, consisting of a derivatization of ketoprofen and long hydrocarbon chain of fatty acids with diacylhydrazine linkage. The presence of an acidic moiety in ketoprofen may lead to ulceration in the gastrointestinal tract that reduces the efficacy of the drug with an increased adverse effect. The synthesis of prodrugs of ketoprofen involves the use of fatty acids as a carrier and hydrazine as a spacer. Synthesized prodrugs were characterized by infrared, 1H-NMR and mass spectroscopy. The resulting prodrugs were found to be insoluble in water and precipitated out in acetonitrile, hexane, benzene, and so on. The synthesized prodrugs are slightly soluble in chloroform, methanol and ethanol and only form a gel like structure in carbon tetrachloride. The resulting gels are referred as organogels and prodrugs are referred to as organogelators. The surface morphology of the prepared organogels were studied by field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM), and other spectral characteristics were also investigated. FE-SEM and TEM images revealed that there were continuous elongated fiber-like structures present that were in the nanometer size range. Gel–sol temperature profiles of the prepared organogels were also studied using differential scanning calorimetry. The results from all these techniques are presented and discussed from point of view of the use of the derivatives as prodrug formulations. It is demonstrated that the prodrug containing the diacylhydrazine moiety has the ability to form a gel.

  利用抗炎药物的前药治疗疾病的策略应用广泛。在本研究中，我们报道了酮洛芬前药的合成，该前药由酮洛芬的衍生化和具有二酰肼键的长碳链脂肪酸组成。酮洛芬中的酸性基团可能导致胃肠道溃疡，这种副作用减少了药物的有效性并增加了不良反应。酮洛芬前药的合成采用了脂肪酸作为载体和肼作为间隔物。合成的前药通过红外、核磁共振和质谱法进行了特征表征。结果显示，这些前药不溶于水，并在乙腈、己烷、苯等溶剂中沉淀出来。它们在氯仿、甲醇和乙醇中略溶，并且仅在四氯化碳中形成凝胶状结构。这些形成的凝胶被称为有机凝胶，前药被称为有机凝胶形成剂。通过场发射扫描电子显微镜（FE-SEM）和透射电子显微镜（TEM）研究了制备的有机凝胶的表面形态，并调查了其他光谱特性。FE-SEM和TEM图像显示存在连续的纳米级长纤维状结构。还使用差示扫描量热法研究了制备的有机凝胶的凝胶-溶胶温度曲线。从使用这些衍生物作为前药配方的角度出发，展示了所有这些技术的结果并进行了讨论。结果表明，含有二酰肼结构的前药具有形成凝胶的能力。
• Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
  作者：Xiaolong Liu、Meng Zhao、Xinjiong Fan、Yao Fu

  DOI：10.1039/d1cy01028j

  日期：——

  mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with high E values were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.

  细菌酯酶是生产光学纯化合物的潜在生物催化剂。然而，酯酶的底物混杂性和手性选择性通常呈负相关，限制了它们的商业价值。在此，一种高效且多功能的酯酶 (Est816) 被确定为一种有前途的催化剂，可用于水解各种具有低对映选择性的经济上重要的底物。我们合理地设计了几种变体，对 2-芳基丙酸乙酯的催化效率提高了 11 倍，主要保留了初始底物范围和对映选择性。这些变体显着提高了生物催化应用的效率。基于最佳变体 Est816-M1，通过对结构信息和分子对接的仔细分析，设计了几种具有更高或反向对映选择性的变体。两个立体选择性互补突变体 Est816-M3 和 Est816-M4 成功克服甚至逆转了低对映选择性，以及几种具有高对映选择性的 2-芳基丙酸衍生物获得了E值。我们的研究结果为制备结构多样的手性羧酸提供了潜在的工业生物催化剂，并进一步为提高酯酶的催化效率和对映选择性奠定了基础。
• Comparison of the enzymatic activity of commercial and semipurified lipase of Candida cylindracea in the hydrolysis of the esters of (R,S) 2-aryl propionic acids.
  作者：María J. Hernáiz、José M. Sanchez-Montero、José V. Sinisterra

  DOI：10.1016/s0040-4020(01)89267-x

  日期：1994.1

  A semipurified lipase of Candida cylindradea (LS) -easily obtained from commercial crude lipase (LC)- is used in the enantioselective hydrolysis of (R,S) 2-arylpropionates. The semipurification treatment diminishes the lipase activity more than the esterase activity. The addition of lactose (24 h) increases both activities. LS is more active than LC -at the same amount of protein- in hydrolysis of

  可以容易地从商业粗脂肪酶（LC）获得的Candida cylindradea（LS）的半纯化脂肪酶用于（R，S）2-芳基丙酸酯的对映选择性水解。半纯化处理比酯酶活性更多地降低了脂肪酶的活性。乳糖的添加（24小时）增加了这两种活性。在（R，S）2-芳基丙酸酯的水解过程中，在蛋白质含量相同的情况下，LS比LC更具活性。该半纯化显示出这些酯的对映体特异性水解的产率显着提高。
• [EN] LONG-ACTING KETOPROFEN COMPOSITIONS<br/>[FR] COMPOSITIONS DE KÉTOPROFÈNE À ACTION PROLONGÉE
  申请人：ZOETIS LLC

  公开号：WO2015095045A1

  公开（公告）日：2015-06-25

  The invention describes a long-acting veterinary composition comprising at least one ketoprofen ester prodrug. The composition also comprises at least one veterinary acceptable triglyceride, and optionally, at least one preservative, and optionally, at least one additional veterinary acceptable excipient. The invention also describes a method of treating an animal for fever, pain, and/or inflammation by administering the long-acting composition comprising at least one ketoprofen ester prodrug to the animal in need thereof.

  该发明描述了一种长效兽医组合物，其中包括至少一种酮洛芬酯前药。该组合物还包括至少一种兽医可接受的甘油三酯，可选地，至少一种防腐剂，以及可选地，至少一种其他兽医可接受的赋形剂。该发明还描述了一种通过向需要治疗发热、疼痛和/或炎症的动物投与至少一种酮洛芬酯前药的长效组合物来治疗动物的方法。