γ-2-(2-(2-azidoethoxy)ethoxy)ethylfolamide | 1471990-06-3

• 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: γ-2-(2-(2-azidoethoxy)ethoxy)ethylfolamide
• 英文别名: Folate-PEG2-Azide；(2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[2-[2-(2-azidoethoxy)ethoxy]ethylamino]-5-oxopentanoic acid
• CAS: 1471990-06-3
• 化学式: C₂₅H₃₁N₁₁O₇
• 分子量: 597.591
• InChiKey: SOKNXMSNQVVXLZ-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.28
• 重原子数：
  43.0
• 可旋转键数：
  18.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  272.3
• 氢给体数：
  6.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  、 γ-2-(2-(2-azidoethoxy)ethoxy)ethylfolamide 以 水 为溶剂， 反应 4.0h， 以11.4 mg的产率得到(2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[2-[2-[2-[13-[4-[4-[[hydroxy-[[hydroxy-[[11-(phosphonomethyl)-1,4,8,11-tetrazabicyclo[6.6.2]hexadecan-4-yl]methyl]phosphoryl]methyl]phosphoryl]methyl]anilino]-4-oxobutanoyl]-3,4,5,13-tetrazatetracyclo[13.4.0.02,6.07,12]nonadeca-1(19),2(6),3,7,9,11,15,17-octaen-5-yl]ethoxy]ethoxy]ethylamino]-5-oxopentanoic acid
  参考文献：
  名称：

  [EN] CYCLAM BASED COMPOUNDS, THEIR CONJUGATES, CO-ORDINATION COMPOUNDS, PHARMACEUTICAL COMPOSITION CONTAINING THEREOF, METHOD OF PREPARATION AND USE THEREOF
  [FR] COMPOSÉS À BASE DE CYCLAME, LEURS CONJUGUÉS, COMPOSÉS DE COORDINATION, COMPOSITION PHARMACEUTIQUE LES CONTENANT, PROCÉDÉ DE PRÉPARATION ET UTILISATION ASSOCIÉS

  摘要：

  基于环戊胺的化合物、其共轭物、配位化合物、含有其的药物组合物、制备方法及使用方法。本发明涉及一般式(I)的基于环戊胺的化合物、这些化合物与共轭基的共轭物、它们的配位化合物、靶向共轭物、基于环戊胺的化合物的制备方法、制备基于环戊胺的化合物的中间产物、含有它们的药物制剂及其用途。

  公开号：

  WO2017084645A1

文献信息

• Folate Receptor-Mediated Enhanced and Specific Delivery of Far-Red Light-Activatable Prodrugs of Combretastatin A-4 to FR-Positive Tumor
  作者：Gregory Nkepang、Moses Bio、Pallavi Rajaputra、Samuel G. Awuah、Youngjae You

  DOI：10.1021/bc500376j

  日期：2014.12.17

  We examined the concept of a novel prodrug strategy in which anticancer drug can be locally released by visible/near IR light, taking advantage of the photodynamic process and photo-unclick chemistry. Our most recently formulated prodrug of combretastatin A-4, Pc-(L-CA4)2, showed multifunctionality for fluorescence imaging, light-activated drug release, and the combined effects of PDT and local chemotherapy. In this formulation, L is a singlet oxygen cleavable linker. Here, we advanced this multifunctional prodrug by adding a tumor-targeting group, folic acid (FA). We designed and prepared four FA-conjugated prodrugs 1-4 (CA4-L-Pc-PEGn-FA: n = 0, 2, 18, ∼45) and one non-FA-conjugated prodrug 5 (CA4-L-Pc-PEG18-boc). Prodrugs 3 and 4 had a longer PEG spacer and showed higher hydrophilicity, enhanced uptake to colon 26 cells via FR-mediated mechanisms, and more specific localization to SC colon 26 tumors in Balb/c mice than prodrugs 1 and 2. Prodrug 4 also showed higher and more specific uptake to tumors, resulting in selective tumor damage and more effective antitumor efficacy than non-FA-conjugated prodrug 5. FR-mediated targeting seemed to be an effective strategy to spare normal tissues surrounding tumors in the illuminated area during treatment with this prodrug.
• Preparation and in Vitro Photodynamic Activities of Folate-Conjugated Distyryl Boron Dipyrromethene Based Photosensitizers
  作者：Mei-Rong Ke、Sin-Lui Yeung、Dennis K. P. Ng、Wing-Ping Fong、Pui-Chi Lo

  DOI：10.1021/jm4009168

  日期：2013.11.14

  Two folate-conjugated diiododistyryl boron dipyrromethenes have been prepared and characterized with various spectroscopic methods. These conjugates exhibit higher photocytotoxicity toward the KB human nasopharyngeal carcinoma cells, which have high expression of folate receptors When compared with the MCF-7 human breast adenocarcinoma cells, which have low expression of folate receptors. The difference in photocytotoxicity for these two cell lines is particularly large for the conjugate with a shorter oligoethylene glycol linker (compound 11a) as a result of its higher cellular uptake and slightly lower aggregation tendency. Its IC50 value toward KB cells (0.06 mu M) is 43-fold lower than analogue with a longer linker (compound 11b). The length compound 11a shows high affinity toward the endoplasmic lysosomes. that for MCF-7 cells, while the difference is only 6-fold for the of the spacer also affects their subcellular localization. While eticulum of KB cells, conjugate 11b is mainly localized in the lysosomes.
• Ligand-Modified Double-Stranded Nucleic Acids
  申请人：Dicerna Pharmaceuticals, Inc.

  公开号：US20170305956A1

  公开（公告）日：2017-10-26

  The invention provides for double stranded nucleic acid molecules comprising a 5′ extension of the sense or antisense strand and further comprising a plurality of nucleotides that are conjugated to a ligand and methods of using the double-stranded nucleic acid molecules. Ligand-modified oligomers where the sense stands form a tetraloop provide new potent and stable RNA interference agents. These dsNA molecules are synthesized using a plurality of nucleotides that include ligand-modified monomers, nucleotide analog monomers, modified nucleotide monomers and the like, using standard nucleotide synthetic methods and systems.