ECO746 | 1312753-43-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ECO746
• 英文别名: (2S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1R)-2-[2-[[[(4S)-4-[[4-[(2-amino-4-imino-3H-pteridin-6-yl)methylamino]benzoyl]amino]-4-carboxybutanoyl]amino]carbamoyloxy]ethyldisulfanyl]-1-carboxyethyl]amino]-1,5-dioxo-5-[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1,5-dioxo-5-[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1,5-dioxo-5-[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentan-2-yl]amino]-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-oxopentanoic acid
• CAS: 1312753-43-7
• 化学式: C₈₇H₁₂₂N₂₆O₄₀S₂
• 分子量: 2236.21
• InChiKey: LVORPMJXJXHOAS-SCFJOVQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -16.6
• 重原子数：
  155
• 可旋转键数：
  70
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  1150
• 氢给体数：
  40
• 氢受体数：
  51

反应信息

• 作为反应物：
  描述：

  ECO746 在 1,4-二巯基-2,3-丁二醇 作用下， 生成 Aminopterin-alpha-hyrazide
  参考文献：
  名称：

  Design and regioselective synthesis of a new generation of targeted therapeutics. Part 3: Folate conjugates of aminopterin hydrazide for the treatment of inflammation

  摘要：

  Efficient syntheses of folate receptor (FR) targeting conjugates of the anti-inflammatory, aminopterin hydrazide, are described. 2-{4-Benzoylamino}-5-oxo-5-{N`-[2-(pyridin-2-yldisulfanyl)-ethoxycarbonyl]-hydrazino}-pentanoic acid is synthesized from commercially available 4-[(2-amino-4-imino-3,4-dihydro-pteridin-6-yl-methyl)-amino]-benzoic acid. Conjugation of this novel, activated aminopterin hydrazide to folic acid through cysteine-terminating (C-terminus), peptide/carbohydrate spacers results in highly water soluble conjugates which allow for the release of free aminopterin hydrazide within the endosomes of targeted cells. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.085
• 作为产物：
  描述：

  Pte-γGlu-(Glu(1-amino-1-deoxy-D-glucitol)-Glu)2-Glu(1-amino-1-deoxy-D-glucitol)-Cys-OH 、 (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]-5-oxo-5-[2-[2-(pyridin-2-yldisulfanyl)ethoxycarbonyl]hydrazinyl]pentanoic acid 在 碳酸氢钠 作用下， 以 二甲基亚砜 为溶剂， 生成 ECO746
  参考文献：
  名称：

  Design and regioselective synthesis of a new generation of targeted therapeutics. Part 3: Folate conjugates of aminopterin hydrazide for the treatment of inflammation

  摘要：

  Efficient syntheses of folate receptor (FR) targeting conjugates of the anti-inflammatory, aminopterin hydrazide, are described. 2-{4-Benzoylamino}-5-oxo-5-{N`-[2-(pyridin-2-yldisulfanyl)-ethoxycarbonyl]-hydrazino}-pentanoic acid is synthesized from commercially available 4-[(2-amino-4-imino-3,4-dihydro-pteridin-6-yl-methyl)-amino]-benzoic acid. Conjugation of this novel, activated aminopterin hydrazide to folic acid through cysteine-terminating (C-terminus), peptide/carbohydrate spacers results in highly water soluble conjugates which allow for the release of free aminopterin hydrazide within the endosomes of targeted cells. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.085

文献信息

• FOLATE CONJUGATES FOR TREATING INFLAMMATION OF THE EYE
  申请人：Leamon Christopher Paul

  公开号：US20130203680A1

  公开（公告）日：2013-08-08

  The present invention relates to methods of use of folate conjugates for treating inflammatory diseases of the eye, to folate conjugates for use in treating inflammatory diseases of the eye, and to folate conjugates for use in the manufacture of a medicament for treating inflammatory diseases of the eye. More particularly, the invention is directed to the use of folate linked to one or more anti-inflammatory agents for each of the above-described uses.

  本发明涉及使用叶酸共轭物治疗眼部炎症疾病的方法，用于治疗眼部炎症疾病的叶酸共轭物，以及用于制造用于治疗眼部炎症疾病的药物的叶酸共轭物。更具体地，本发明针对上述用途中的每一种，使用叶酸与一个或多个抗炎药物相连的方法。
• VITAMIN RECEPTOR DRUG DELIVERY CONJUGATES FOR TREATING INFLAMMATION
  申请人：Endocyte, Inc.

  公开号：US20150314015A1

  公开（公告）日：2015-11-05

  Described herein are compositions, methods, compounds, conjugates, and kits for use in targeted drug delivery using drug delivery conjugates containing hydrophilic spacer linkers for use in treating disease states caused by pathogenic cell populations, such as inflammatory cells.

  本文描述了用于靶向药物传递的组合物、方法、化合物、共轭物和试剂盒，其中包含亲水性空间连接剂的药物传递共轭物，用于治疗由病原细胞群引起的疾病状态，例如炎症细胞。
• Methods for treating cancer using combination therapies
  申请人：Endocyte, Inc.

  公开号：US10010618B2

  公开（公告）日：2018-07-03

  Described are methods, uses, and kits for utilizing a targeted ligand conjugate in combination with a thiol inhibitor or a system xc− inhibitor for the treatment of cancer or inflammation. Also described are in vitro assays utilizing a targeted ligand conjugate in combination with a thiol inhibitor or a system xc− inhibitor.

  描述了利用靶向配体共轭物与硫醇抑制剂或系统 xc- 抑制剂结合治疗癌症或炎症的方法、用途和试剂盒。还描述了利用靶向配体共轭物与硫醇抑制剂或系统 xc- 抑制剂结合的体外试验。
• METHODS FOR TREATING CANCER USING COMBINATION THERAPIES
  申请人：Endocyte, Inc.

  公开号：US20160296630A1

  公开（公告）日：2016-10-13

  Described are methods, uses, and kits for utilizing a targeted ligand conjugate in combination with a thiol inhibitor or a system x c − inhibitor for the treatment of cancer or inflammation. Also described are in vitro assays utilizing a targeted ligand conjugate in combination with a thiol inhibitor or a system x c − inhibitor.
• Design and regioselective synthesis of a new generation of targeted therapeutics. Part 3: Folate conjugates of aminopterin hydrazide for the treatment of inflammation
  作者：Iontcho R. Vlahov、Fei You、Hari Krishna R. Santhapuram、Yu Wang、Jeremy F. Vaughn、Spencer J. Hahn、Paul J. Kleindl、Mingjin Fan、Christopher P. Leamon

  DOI：10.1016/j.bmcl.2010.12.085

  日期：2011.2

  Efficient syntheses of folate receptor (FR) targeting conjugates of the anti-inflammatory, aminopterin hydrazide, are described. 2-4-Benzoylamino}-5-oxo-5-N`-[2-(pyridin-2-yldisulfanyl)-ethoxycarbonyl]-hydrazino}-pentanoic acid is synthesized from commercially available 4-[(2-amino-4-imino-3,4-dihydro-pteridin-6-yl-methyl)-amino]-benzoic acid. Conjugation of this novel, activated aminopterin hydrazide to folic acid through cysteine-terminating (C-terminus), peptide/carbohydrate spacers results in highly water soluble conjugates which allow for the release of free aminopterin hydrazide within the endosomes of targeted cells. (c) 2010 Elsevier Ltd. All rights reserved.