ethyl 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoate | 116314-52-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoate
• 英文别名: ethyl 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylate
• CAS: 116314-52-4
• 化学式: C₁₂H₁₀N₂O₆
• 分子量: 278.221
• InChiKey: KZGBADQGBKGUGS-UHFFFAOYSA-N

物化性质

• 沸点：
  457.2±45.0 °C(Predicted)
• 密度：
  1.501±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoate 在 sodium borohydrid 作用下， 以 乙醇 为溶剂， 以0.55 g (75%)的产率得到2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)propanol
  参考文献：
  名称：

  Pharmacologically active compounds, methods for the preparation thereof

  摘要：

  公式I的药理活性儿茶酚衍生物，其中R.sub.1和R.sub.2独立地包括氢、烷基、酰基、可选择地取代的芳酰基、较低的烷基磺酰基或烷基氨基甲酰基，或者一起形成较低的烷基亚甲基或环烷基亚甲基，X包括电负取代基，如卤素、硝基、氰基、较低的烷基磺酰基、磺胺基、醛基、羧基或三氟甲基，R.sub.3包括氢、卤素、羟基烷基、氨基、硝基、氰基、三

  公开号：

  US04963590A1
• 作为产物：
  描述：

  ethyl 2-cyano-3-(3-hydroxy-4-methoxy-5-nitrophenyl)prop-2-enoate 在 三乙胺 、 氢碘酸 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 以48%的产率得到ethyl 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoate
  参考文献：
  名称：

  恩他卡朋的新合成方法及相关研究报告

  摘要：

  儿茶酚-O-甲基转移酶（COMT）抑制剂entacapone（E-异构体）的新合成是在温和条件下通过胺介导的前体2-Cyano-3-（3-羟基-4-甲氧基- 5-硝基苯基）丙-2-烯酰胺，其中与硝基相邻的甲氧基在亲核攻击下脱甲基。在2-氰基-3-（3,4-二甲氧基-5-硝基苯基）丙酸烯乙酯，2-氰基-3-（3,4-二甲氧基-5-硝基苯基）-N，N上实现了类似的脱甲基-二乙基丙-2-烯酰胺，2-氰基-3-（3-羟基-4-甲氧基-5-硝基苯基）丙酸2-烯酸酯和2-氰基-3-（4-甲氧基-3-硝基苯基）丙酸乙酯-2-烯酸酯。已经研究了脱甲基的范围。2-氰基-3-（3，4-二甲氧基-5-硝基苯基）丙-2-烯酸酯的类似物，其中甲氧基不与NO 2相邻基团不受影响并且酚衍生物产生胺盐。恩他卡朋已与有机碱转化为盐。已经建立了戊酮（Z-异构体）的异构体（Z-异构体的重要人类代谢产物）的晶体结构。主要通过研究质子耦合的13

  DOI：

  10.1007/s12039-015-0961-4

文献信息

• Synthesis of some novel potent and selective catechol O-methyltransferase inhibitors
  作者：Reijo Backstrom、Erkki Honkanen、Aino Pippuri、Pekka Kairisalo、Jarmo Pystynen、Kalevi Heinola、Erkki Nissinen、Inge Britt Linden、Pekka T. Mannisto

  DOI：10.1021/jm00124a017

  日期：1989.4

  A series of disubstituted catechol derivatives was synthesized and tested as potential COMT inhibitors. The most active compounds were more than 1000 times more potent (IC50 = 3-6 nM) in vitro than the known COMT inhibitor, 3',4'-dihydroxy-2-methylpropiophenone (U 0521, IC50 = 6000 nM). The new compounds were also highly selective COMT inhibitors with no activity against other essential enzymes involved

  合成了一系列二取代的邻苯二酚衍生物，并测试了其作为潜在的COMT抑制剂的能力。活性最高的化合物在体外的效价（IC50 = 3-6 nM）比已知的COMT抑制剂3'，4'-二羟基-2-甲基苯乙酮（U 0521，IC50 = 6000 nM）高出1000倍以上。新化合物也是高度选择性的COMT抑制剂，对儿茶酚胺的合成和代谢中涉及的其他必需酶没有活性。
• Pharmacologically active catechol derivatives
  申请人：Orion-yhtyma Oy

  公开号：US05446194A1

  公开（公告）日：1995-08-29

  A compound according to formula 1 ##STR1## wherein R.sub.1 and R.sub.2 independently represent hydrogen, carbamoyl which is substituted by an alkyl of 1 to 4 carbon atoms, alkylcarbonyl of 2 to 5 carbon atoms or phenyl carbonyl, X represents halogen nitro or cyano and R.sub.3 represents ##STR2## wherein R.sub.4 represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R.sub.5 represents carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms or which is substituted with hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable esters and salts thereof, and a pharmaceutically acceptable carrier therefor, as well as pharmaceutical compositions containing said compounds as COMT inhibitors.

  根据公式1，化合物的结构为：##STR1## 其中，R.sub.1和R.sub.2独立地表示氢、被1到4个碳原子的烷基取代的氨基甲酰基、2到5个碳原子的烷基羰基或苯基羰基，X表示卤素、硝基或氰基，而R.sub.3表示##STR2## 其中，R.sub.4表示氰基或2到5个碳原子的烷基羰基，R.sub.5表示未取代或被1到8个碳原子的烷基取代的氨基甲酰基，或被1到8个碳原子的羟基烷基取代的氨基甲酰基，或药学上可接受的酯和盐，以及其药学上可接受的载体。此外，还包括将该化合物作为COMT抑制剂的药物组合物。
• Method of treating Parkinson's Disease using pentanedione derivatives
  申请人：Orion-yhtyma Oy

  公开号：US05112861A1

  公开（公告）日：1992-05-12

  The invention concerns a method for the treatment of Parkinson's Disease. The method comprises administering a catechol-O-methyl-transferase inhibiting amount of a compound having the formula I ##STR1## wherein R.sub.1 and R.sub.2 independently represent hydrogen, alkylcarbamoyl of 2 to 5 carbon atoms or alkylcarbonyl of 2 to 5 carbon atoms, X represents nitro or cyano and R.sub.3 represents ##STR2## wherein R.sub.4 represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R.sub.5 represents cyano; alkylcarbonyl of 2 to 5 carbon atoms; or carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms, or hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable salts or esters thereof; and a sufficient amount of levodopa to treat Parkinson's Disease. A peripheral decarboxylase inhibitor such as carbidopa or benzerazide is also preferably administered.

  本发明涉及一种治疗帕金森病的方法。该方法包括向患者施用一种具有以下式子I的化合物，其中R1和R2独立地表示氢、2至5个碳原子的烷基氨基酰基或2至5个碳原子的烷基羰基，X表示硝基或氰基，R3表示下列式子：其中R4表示氰基或2至5个碳原子的烷基羰基，R5表示氰基、2至5个碳原子的烷基羰基、未取代或取代了1至8个碳原子的烷基、1至8个碳原子的羟基烷基的氨基甲酰基或其药学上可接受的盐或酯；以及足够的左旋多巴治疗帕金森病。此外，最好还要施用周围脱羧酶抑制剂，如卡比多巴或苯扎酰胺。
• Novel triethylamine mediated thermal reactions of 3-aryl-2-cyanoprop-2-enoic acid derivatives—demethylation, reduction and vinylogation
  作者：Attimogae Shivamurthy Harisha、Suresh Parameshwar Nayak、Kuppuswamy Nagarajan、Tayur Narasingarow Guru Row、Amar A. Hosamani

  DOI：10.1016/j.tetlet.2015.01.148

  日期：2015.3

  3-Aryl-2-propenoic acid derivatives undergo interesting reactions with hot triethylamine. Substrates like 6 having a methoxyl with a nitro in the ortho and cyanoacrylic derivatives in the para positions give O-demethylated products, for example, entacapone 7. On the other hand compounds like 16 having the NO2 in the para and cyanoacrylic in the ortho position undergo reduction and vinylogation. The latter phenomenon is observed in the absence of the NO2 group also. (C) 2015 Elsevier Ltd. All rights reserved.
• Pharmacologically active compounds, methods for the preparation thereof
  申请人：Orion-yhtyma Oy

  公开号：US04963590A1

  公开（公告）日：1990-10-16

  Pharmacologically active catechol derivatives of formula I ##STR1## wherein R.sub.1 and R.sub.2 independently comprise hydrogen, alkyl, acyl, optionally substituted aroyl, lower alkylsulfonyl or alkylcabamoyl or taken together form a lower alkylidene or cycloalkylidene, X comprises an electronegative substituent such as halogen, nitro, cyano, lower alkylsulfonyl, sulfonamido, aldehyde, caboxyl or trifluoromethyl and R.sub.3 comprises hydrogen, halogen, hydroxy alkyl, amino, nitro, cyano, trifluoromethyl, lower alkylsulfonyl, sulfonamide, aldehyde, alkyl carbonyl, aralkylidene carbonyl or carboxyl or a group selected from ##STR2## wherein R.sub.4 comprises hydrogen, alkyl, cyano, carboxyl or acyl and R.sub.5 comprises hydrogen, cyano, carboxyl, alkoxycarbonyl, carboxyalkenyl, nitro, acyl, optionally substituted aroyl or heteroaroyl, hydroxyalkyl or carboxyalkyl or R.sub.4 and R.sub.5 together form a five to seven membered substituted cycloalkanone ring; --(CO).sub.n (CH.sub.2).sub.m --COR wherein n is 0-1 and m is 0-7 and R comprises hydroxy, alkyl, carboxyalkyl, optionally substituted alkene, alkoxy or optionally substituted amino; ##STR3## wherein R.sub.8 and R.sub.9 independently comprise hydrogen or one of the following optionally substituted groups; alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or together form an optionally substituted piperidyl group; --NH--CO--R.sub.10 wherein R.sub.10 comprises a substituted alkyl group.

  公式I的药理活性儿茶酚衍生物，其中R.sub.1和R.sub.2独立地包括氢、烷基、酰基、可选择地取代的芳酰基、较低的烷基磺酰基或烷基氨基甲酰基，或者一起形成较低的烷基亚甲基或环烷基亚甲基，X包括电负取代基，如卤素、硝基、氰基、较低的烷基磺酰基、磺胺基、醛基、羧基或三氟甲基，R.sub.3包括氢、卤素、羟基烷基、氨基、硝基、氰基、三