(Z)-2-(3-ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide | 1451878-43-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: (Z)-2-(3-ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide
• 英文别名: Z-BOX A；2-[(2Z)-3-ethenyl-4-methyl-5-oxo-2,5-dihydro-1H-pyrrol-2-ylidene]acetamide；(2Z)-2-(3-ethenyl-4-methyl-5-oxopyrrol-2-ylidene)acetamide
• CAS: 1451878-43-5
• 化学式: C₉H₁₀N₂O₂
• 分子量: 178.191
• InChiKey: OUFUEOCARHOWCD-DAXSKMNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (Z)-2-(3-ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide 生成 (E)-2-(3-ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide
  参考文献：
  名称：

  Total Synthesis and Detection of the Bilirubin Oxidation Product (Z)-2-(3-Ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide (Z-BOX A)

  摘要：

  The selective total synthesis of the pure Z-isomer of BOX A (8a), a product of oxidative heme degradation with significant physiological impact, was achieved in four to six steps starting from 3-bromo-4-methylfuran-2,5-dione (1). Z-BOX A forms a strong hydrogen bridge framework in the crystalline state. LC-MS techniques allow identification and characterization of isomeric forms of BOX A.

  DOI：

  10.1021/ol402221b
• 作为产物：
  描述：

  3-溴-4-甲基呋喃-2,5-二酮 在 bis-triphenylphosphine-palladium(II) chloride 、 ammonium hydroxide 、 ammonium acetate 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 528.0h， 生成 (Z)-2-(3-ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide
  参考文献：
  名称：

  Total Synthesis and Detection of the Bilirubin Oxidation Product (Z)-2-(3-Ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide (Z-BOX A)

  摘要：

  The selective total synthesis of the pure Z-isomer of BOX A (8a), a product of oxidative heme degradation with significant physiological impact, was achieved in four to six steps starting from 3-bromo-4-methylfuran-2,5-dione (1). Z-BOX A forms a strong hydrogen bridge framework in the crystalline state. LC-MS techniques allow identification and characterization of isomeric forms of BOX A.

  DOI：

  10.1021/ol402221b

文献信息

• BOX A-type monopyrrolic heterocycles modified <i>via</i> the <i>Suzuki-Miyaura</i> cross-coupling reaction
  作者：Daniel Schulze、Maurice Klopfleisch、Helmar Görls、Matthias Westerhausen

  DOI：10.1515/znb-2019-0125

  日期：2020.2.25

  The in vivo oxidation of heme yields bilirubin which is further degraded to the bilirubin oxidation end products (BOXes) that are biologically highly active. To study the mode of action and fate of (Z)-2-(4-methyl-5-oxo-3-vinyl-1,5-dihydro-2H-pyrrol-2-ylidene)acetamide (BOX A), the Suzuki-Miyaura cross-coupling reaction allows to introduce various alkenyl- and aryl-substituents in 3-position of the (Z)-2-(4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)acetamides (BOX A-type monopyrroles). The influence of these groups on structural and NMR-spectroscopic parameters of the central monopyrrolic system is negligible. Special focus has been given to derivatives with 3-positioned aryl substituents carrying trifluoromethyl groups for future in vivo ¹⁹F NMR studies.

  血红素的体内氧化产生胆红素，进一步降解为生物活性极高的胆红素氧化终产物（BOXes）。为了研究（Z）-2-（4-甲基-5-氧代-3-乙烯基-1,5-二氢-2H-吡咯-2-基）乙酰胺（BOX A）的作用方式和命运，Suzuki-Miyaura交叉偶联反应允许在（Z）-2-（4-甲基-5-氧代-1,5-二氢-2H-吡咯-2-基）乙酰胺（BOX A型单吡咯）的3位引入各种烯基和芳基取代基。这些基团对中心单吡咯系统的结构和NMR光谱参数的影响微不足道。特别关注具有3位芳基取代基的衍生物，这些芳基取代基携带三氟甲基基团，以进行未来的体内19F NMR研究。

• Isolation and Identification of Intermediates of the Oxidative Bilirubin Degradation
  作者：Marcel Ritter、Raphael A. Seidel、Peter Bellstedt、Bernd Schneider、Michael Bauer、Helmar Görls、Georg Pohnert

  DOI：10.1021/acs.orglett.6b02287

  日期：2016.9.2

  Four endogenous products of oxidative bilirubin degradation were isolated and fully characterized. The constitutional isomers belong to the propentdyopents (PDPs). Their structures and further oxidative transformations to biologically active bilirubin oxidation end products (Z-BOXes) are reported. Using liquid chromatography–mass spectrometry protocols, PDPs were detected in human bile and gallstones

  氧化胆红素降解的四个内源性产物被分离并得到充分表征。组成异构体属于propentdyopents（PDP）。据报道它们的结构和进一步的氧化转化为生物活性胆红素氧化终产物（Z- BOXes）。使用液相色谱-质谱联用规程，在人的胆汁和胆结石中检测到了PDP。鉴于最近对将BOX作为脑血管痉挛和肝功能障碍的效应子的兴趣，共同出现的PDP代表了要考虑的另一种潜在活性化合物。
• Degradation fragments
  申请人：——

  公开号：US20030162826A1

  公开（公告）日：2003-08-28

  A pharmaceutical composition comprising a compound of formula (I) wherein X is an electron withdrawing group, Y 1 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, —SO 2 R 4 , —CO 2 R 4 , —CONHR 4 or —COR 4 , and each of R 1 , R 2 and R 4 , which may be the same or different, is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocyclyl, or a compound of formula (II) wherein each of Y 2 and Y 3 , which may be the same or different, is hydrogen, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, —SO 2 R 9 , —CO 2 R 9 , —CONHR 9 or —COR 9 , Z is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclyl, —CH═C(NHR 10 )CH((CH 2 ) m CO 2 R 11 )(C═O)CH 3 or —CH 2 (C═O)CH((CH 2 ) m CO 2 R 11 )(C═O)CH 3 , R 8 is —(CH 2 ),CO 2 R 12 , each of R 5 to R 7 and R 9 to R 12 , which may be the same or different, is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocyclyl, and each of m and n, which may be the same or different, is 1 to 6 or a compound of formula (III) wherein each of Y 4 to Y 6 , which may be the same or different, is hydrogen, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, —SO 2 R 19 , —CO 2 R 19 , —CONHR 19 or —COR 19 , each of R 16 and R 17 , which may be the same or different, is —(CH 2 ) p CO 2 R 20 , each of R 13 TO R 15 and R 18 to R 20 , which may be the same or different, is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocyclyl, and p is 1 to 6, or other photolabile degradation product of bilirubin or biliverdin or derivative of a photolabile degradation fragment of bilirubin or biliverdin, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent. 1

  一种药物组合物，包含式 (I) 的化合物，其中 X 是一个电子僻取基团，Y 1 是氢、烷基、烯基、炔基、芳基、杂环基、-SO 2 R 4 、-CO 2 R 4 、-CONHR 4 或-COR 4 和每个 R 1 , R 2 和 R 4 可以相同或不同，为氢、烷基、环烷基、烯基、环烯基、炔基、芳基或杂环烷基，或式 (II) 的化合物，其中每个 Y 2 和 Y 3 可以相同或不同，为氢、烷基、烯基、环烷基、炔基、芳基、杂环基、-SO 2 R 9 、-CO 2 R 9 , -CONHR 9 或-COR 9 , Z 是氢、烷基、环烷基、烯基、环烯基、炔基、芳基、杂环基、-CH═C(NHR 10 )CH((CH 2 ) m CO 2 R 11 )(C═O)CH 3 或-CH 2 (C═O)CH((CH 2 ) m CO 2 R 11 )(C═O)CH 3 , R 8 是-(CH 2 ）、CO 2 R 12 ，R 5 至 R 7 和 R 9 至 R 12 可相同或不同，为氢、烷基、环烷基、烯基、环烯基、炔基、芳基或杂环基，且 m 和 n（可相同或不同）各为 1 至 6 或式 (III) 化合物，其中 Y 4 至 Y 6 可以相同或不同，为氢、烷基、烯基、炔基、芳基、杂环基、-SO 2 R 19 、-CO 2 R 19 、-CONHR 19 或-COR 19 ，每个 R 16 和 R 17 可以相同或不同，是-(CH 2 ) p CO 2 R 20 ，R 13 至 R 15 和 R 18 至 R 20 可以是相同或不同的氢、烷基、环烷基、烯基、环烯基、炔基、芳基或杂环烷基，且 p 为 1 至 6，或胆红素或胆绿素的其他光降解产物或胆红素或胆绿素的光降解片段的衍生物，或其药学上可接受的盐，连同药学上可接受的载体或稀释剂。 1
• BILIRUBIN OR BILIVERDIN DEGRADATION FRAGMENTS
  申请人：MEDICAL RESEARCH COUNCIL

  公开号：EP1272178B1

  公开（公告）日：2008-01-23
• US7098238B2
  申请人：——

  公开号：US7098238B2

  公开（公告）日：2006-08-29