allyl 1-(4-(O-4-nitrophenyloxycarbonyl)methyl-2-nitrophenyl)-2,3,4-tri-O-allyloxycarbonyl-β-D-glucuronate | 1353003-36-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: allyl 1-(4-(O-4-nitrophenyloxycarbonyl)methyl-2-nitrophenyl)-2,3,4-tri-O-allyloxycarbonyl-β-D-glucuronate
• 英文别名: prop-2-en-1-yl (2S,3S,4S,5R,6S)-6-(2-nitro-4-{[(4-nitrophenoxycarbonyl)oxy]methyl}phenoxy)-3,4,5-tris({[(prop-2-en-1-yloxy)carbonyl]oxy})oxane-2-carboxylate；prop-2-enyl (2S,3S,4S,5R,6S)-6-[2-nitro-4-[(4-nitrophenoxy)carbonyloxymethyl]phenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate
• CAS: 1353003-36-7
• 化学式: C₃₅H₃₄N₂O₂₀
• 分子量: 802.656
• InChiKey: XHIHWXBVEDTGNG-WCDZDMCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  57
• 可旋转键数：
  26
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  279
• 氢给体数：
  0
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  allyl 1-(4-(O-4-nitrophenyloxycarbonyl)methyl-2-nitrophenyl)-2,3,4-tri-O-allyloxycarbonyl-β-D-glucuronate 在 吗啉 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 (2S,3S,4S,5R,6S)-6-[4-[[2-[[2-(5-fluoro-4-methylpyridin-3-yl)-5-(4-methyl-6-methylsulfonylpyridin-3-yl)indole-1-carbonyl]-methylamino]ethyl-methylcarbamoyl]oxymethyl]-2-nitrophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
  参考文献：
  名称：

  Prodrugs of a JAK Inhibitor Compound for Treatment of Gastrointestinal Inflammatory Disease

  摘要：

  本发明提供了一种前药化合物，它是针对哺乳动物胃肠道靶向输送JAK抑制剂的前药。本发明还提供了包含该化合物的药物组合物，使用该化合物治疗胃肠道炎症性疾病的方法，以及用于制备该化合物的过程和中间体。

  公开号：

  US20170145044A1
• 作为产物：
  描述：

  allyl 1-(4-(tert-butyldimethylsilyloxy)methyl-2-nitrophenyl)-β-D-glucuronate 在 吡啶 、 氟化氢吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 生成 allyl 1-(4-(O-4-nitrophenyloxycarbonyl)methyl-2-nitrophenyl)-2,3,4-tri-O-allyloxycarbonyl-β-D-glucuronate
  参考文献：
  名称：

  一种用于癌症三联疗法的异二聚体葡糖醛酸前体药物：化学放大器的双重作用

  摘要：

  放大动作！我们开发了第一个治疗性靶向系统，该系统包括一个化学放大器，该放大器经过编程，既可以在一个酶促激活步骤后释放两种有效的抗癌药物，又可以在扩增过程完成后本身就具有细胞毒性。

  DOI：

  10.1002/cmdc.201100355

文献信息

• Antineoplastic Agents. 600. From the South Pacific Ocean to the Silstatins
  作者：George R. Pettit、Pablo M. Arce、Jean-Charles Chapuis、Christian B. Macdonald

  DOI：10.1021/np501004h

  日期：2015.3.27

  The recent advances in the development of antibody and other drug conjugates for targeted cancer treatment have further increased the need for powerful cancer cell growth inhibitors. Toward that objective we have extended our earlier discovery of the remarkable anticancer bacillistatins 1 and 2 from Bacillus silvestris to SAR and other structural modifications such as availability of a free hydroxy group for antibody-drug conjugate (ADC) and other prodrug linkage. That direction has resulted in seven structural modifications designated silstatins 1-8 (7a, 8a, 8b, 14a, 15a, 15b, 18a, and 18b), where the exceptional cancer cell growth inhibition of some of them are in the range GI(50) 10(-3)-10(-4) mu M/mL. Silstatin 7 (18a) was converted to a glucuronic conjugate (28) that displayed an impressive reduction in toxicity during transport.
• [EN] PRODRUGS OF A JAK INHIBITOR COMPOUND FOR TREATMENT OF GASTROINTESTINAL INFLAMMATORY DISEASE<br/>[FR] PROMÉDICAMENTS D'UN COMPOSÉ INHIBITEUR DE JAK POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES GASTRO-INTESTINALES
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2017091544A1

  公开（公告）日：2017-06-01

  The invention provides compounds of formula (I) which are prodrugs of a JAK inhibitor agent for the targeted delivery of the JAK inhibitor to the gastrointestinal tract of a mammal. The invention also provides pharmaceutical compositions comprising the compounds, methods of using the compounds to treat gastrointestinal inflammatory diseases, and processes and intermediates useful for preparing the compounds.
• [EN] LINKERS FOR USE IN ANTIBODY DRUG CONJUGATES<br/>[FR] LIEURS DESTINÉS À ÊTRE UTILISÉS DANS DES CONJUGUÉS ANTICORPS-MÉDICAMENT
  申请人：[en]ORUM THERAPEUTICS, INC.

  公开号：WO2023037268A1

  公开（公告）日：2023-03-16

  The present disclosure provides traceless linkers, which can link an inducer of protein-protein interaction to a cell binding agent. Also provided are compositions comprising the linked compounds. The compounds and compositions are useful for treating diseases such as cancer in subjects in need thereof.