methyl {[2-(hydroxymethyl)-4-nitrophenyl] 2,3,4-tri-O-acetyl-β-D-glucopyranosid}uronate | 148579-84-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl {[2-(hydroxymethyl)-4-nitrophenyl] 2,3,4-tri-O-acetyl-β-D-glucopyranosid}uronate
• 英文别名: I(2)-D-Glucopyranosiduronic acid, 2-(hydroxymethyl)-4-nitrophenyl, methyl ester, 2,3,4-triacetate；methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[2-(hydroxymethyl)-4-nitrophenoxy]oxane-2-carboxylate
• CAS: 148579-84-4
• 化学式: C₂₀H₂₃NO₁₃
• 分子量: 485.402
• InChiKey: BKXLQKMYILRJKC-KVIJGQROSA-N

物化性质

• 沸点：
  599.3±50.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  190
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl {[2-(hydroxymethyl)-4-nitrophenyl] 2,3,4-tri-O-acetyl-β-D-glucopyranosid}uronate 在 甲醇 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.5h， 生成 methyl (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[2-[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]carbamoyloxymethyl]-4-nitrophenoxy]oxane-2-carboxylate
  参考文献：
  名称：

  蒽环类前药用于抗体指导的酶前药治疗。

  摘要：

  报道了柔红霉素和阿霉素的一系列新前药，它们是抗体指导的酶前药治疗（ADEPT）的候选药物。这些化合物（25a，b，c和32a，b，c）经设计可在被β-葡萄糖醛酸苷酶激活后产生细胞毒性药物。如所期望的，在大肠杆菌β-葡糖醛酸糖苷酶以及从人β-葡糖醛酸糖苷酶和人源化CEA特异性结合区获得的融合蛋白进行酶促切割后，观察到活性药物的回收。这六种前药对鼠L1210细胞系的稳定性高，比阿霉素的细胞毒性低100倍以上。邻位取代的氨基甲酸苯酯25a，b，c比相应的对位取代的类似物更好地是β-葡萄糖醛酸苷酶的底物。

  DOI：

  10.1021/jm970589l
• 作为产物：
  描述：

  5-硝基水杨醛 在 sodium tetrahydroborate 、 silica gel 、 silver(l) oxide 作用下， 以 氯仿 、 异丙醇 、 乙腈 为溶剂， 反应 4.75h， 生成 methyl {[2-(hydroxymethyl)-4-nitrophenyl] 2,3,4-tri-O-acetyl-β-D-glucopyranosid}uronate
  参考文献：
  名称：

  蒽环类前药用于抗体指导的酶前药治疗。

  摘要：

  报道了柔红霉素和阿霉素的一系列新前药，它们是抗体指导的酶前药治疗（ADEPT）的候选药物。这些化合物（25a，b，c和32a，b，c）经设计可在被β-葡萄糖醛酸苷酶激活后产生细胞毒性药物。如所期望的，在大肠杆菌β-葡糖醛酸糖苷酶以及从人β-葡糖醛酸糖苷酶和人源化CEA特异性结合区获得的融合蛋白进行酶促切割后，观察到活性药物的回收。这六种前药对鼠L1210细胞系的稳定性高，比阿霉素的细胞毒性低100倍以上。邻位取代的氨基甲酸苯酯25a，b，c比相应的对位取代的类似物更好地是β-葡萄糖醛酸苷酶的底物。

  DOI：

  10.1021/jm970589l

文献信息

• [EN] EPOTHILONE ANALOGS FOR SITE SPECIFIC DELIVERY IN THE TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] ANALOGUES D'EPOTHILONE PERMETTANT L'ADMINISTRATION SPECIFIQUE D'UN SITE DANS LE TRAITEMENT DE MALADIES PROLIFERATIVES
  申请人：SCHERING AG

  公开号：WO2004050089A1

  公开（公告）日：2004-06-17

  Conjugates of epothilones and epothilone derivatives (as effectors) with suitable saccharides or saccharide derivatives (as recognition units) are described. Their production is carried out by the recognition units being reacted with suitable linkers, and the compounds that are produced are conjugated to the effectors. The pharmaceutical use of the conjugates for treating proliferative or angiogenesis-associated processes is described.

  本文描述了用适当的糖或糖衍生物（作为识别单元）与紫杉醇类和紫杉醇衍生物（作为效应物）的共轭体。它们的生产是通过将识别单元与适当的连接剂反应，然后将产生的化合物与效应物共轭。本文还描述了共轭体在治疗增殖或血管生成相关过程中的药物用途。
• Effector conjugates, methods for their preparation and their pharmaceutical use
  申请人：——

  公开号：US20040167083A1

  公开（公告）日：2004-08-26

  Conjugates of epothilones and epothilone derivatives (as effectors) with suitable saccharides or saccharide derivatives (as recognition units) are described. Their production is carried out by the recognition units being reacted with suitable linkers, and the compounds that are produced are conjugated to the effectors. The pharmaceutical use of the conjugates for treating proliferative or angiogenesis-associated processes is described.

  描述了具有适当的糖或糖衍生物（作为识别单元）的紫杉醇和紫杉醇衍生物（作为效应物）的共轭物。它们的制备是通过将识别单元与适当的连接剂反应，然后将产生的化合物与效应物共轭。描述了共轭物在治疗增殖或血管生成相关过程方面的药物应用。
• New effector conjugates, methods for their preparation and their pharmaceutical use
  申请人：Bosslet Klaus

  公开号：US20060276413A1

  公开（公告）日：2006-12-07

  Conjugates of epothilones and epothilone derivatives (as effectors) with suitable saccharides or saccharide derivatives (as recognition units) are described. Their production is carried out by the recognition units being reacted with suitable linkers, and the compounds that are produced are conjugated to the effectors. The pharmaceutical use of the conjugates for treating proliferative or angiogenesis-associated processes is described.

  本文描述了与适当的糖或糖衍生物（作为识别单元）结合的依泊单酮及其衍生物的共轭物（作为效应物）。它们的生产是通过将识别单元与适当的连接剂反应，然后将产生的化合物与效应物结合而完成的。本文还描述了这些共轭物在治疗增殖或血管生成相关过程中的药物用途。
• 2-Nitro and 4-nitro-quinone-methides are not irreversible inhibitors of bovine β-glucuronidase
  作者：Michel Azoulay、Frédéric Chalard、Jean-Pierre Gesson、Jean-Claude Florent、Claude Monneret

  DOI：10.1016/s0008-6215(01)00083-0

  日期：2001.5

  4-Benzylamino-(and 4-chloromethyl)-2-nitro-beta -D-glucuronides (4, 10) and their 2-substituted-4-nitro regioisomers (7, 13) were prepared by glycosidation of the 3-nitro-4-hydroxy- and the 2-hydroxy-5-nitro-benzylic alcohol, respectively, with a glucuronyl donor. Carbonate activation followed by reaction with benzylamine or methanesulfonyl chloride afforded, after complete deprotection, the target molecules 4, 7, 10 and 13. These compounds have been synthesized to determine whether these molecules are (or not) glucuronidase inhibitors. After incubation with bovine liver beta -glucuronidase, none of the cleavage products (the titled quinone-methides) showed to be irreversible inhibitors of this enzyme. (C) 2001 Published by Elsevier Science Ltd.
• EPOTHILONE ANALOGS FOR SITE SPECIFIC DELIVERY IN THE TREATMENT OF PROLIFERATIVE DISEASES
  申请人：Schering AG

  公开号：EP1581218A1

  公开（公告）日：2005-10-05