α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folic acid | 292045-47-7

• 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: α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folic acid
• 英文别名: (4S)-5-oxo-4-[[4-[[4-oxo-2-(2-trimethylsilylethoxycarbonylamino)-3H-pteridin-6-yl]methylamino]benzoyl]amino]-5-(2-trimethylsilylethoxy)pentanoic acid
• CAS: 292045-47-7
• 化学式: C₃₀H₄₃N₇O₈Si₂
• 分子量: 685.885
• InChiKey: FVDFZHPRWZJASH-QFIPXVFZSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.06
• 重原子数：
  47
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  210
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  A step-wise synthetic approach is necessary to access γ-conjugates of folate: folate-conjugated prodigiosenes

  摘要：

  尽管有大量的文献描述了将叶酸与药效团反应，但这种方法无法有效地提供所需的共轭物的正确位置异构体。

  DOI：

  10.1039/c9ra01435g
• 作为产物：
  描述：

  (S)-2-tert-Butoxycarbonylamino-pentanedioic acid 5-benzyl ester 1-(2-trimethylsilanyl-ethyl) ester 在 palladium on activated charcoal 、 氢气 、 对甲苯磺酸 、 7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 26.0h， 生成 α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folic acid
  参考文献：
  名称：

  A step-wise synthetic approach is necessary to access γ-conjugates of folate: folate-conjugated prodigiosenes

  摘要：

  尽管有大量的文献描述了将叶酸与药效团反应，但这种方法无法有效地提供所需的共轭物的正确位置异构体。

  DOI：

  10.1039/c9ra01435g

文献信息

• [EN] SYNTHESIS AND UTILITY OF NEW CAPGROUP LARGAZOLE ANALOGS<br/>[FR] SYNTHÈSE ET UTILISATION DE NOUVEAUX ANALOGUES DE LARGAZOLE
  申请人：UNIV COLORADO STATE RES FOUND

  公开号：WO2016144814A1

  公开（公告）日：2016-09-15

  Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

  本文描述了类似largazole的类似物。此外，还描述了使用类似largazole和含有类似物的药物组合物治疗癌症、血液疾病、自身免疫疾病和阿尔茨海默病的方法。同样描述了制备类似largazole的方法。
• INACTIVATORS OF O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE
  申请人：Moschel Robert C.

  公开号：US20100204172A1

  公开（公告）日：2010-08-12

  Disclosed are compounds that are AGT inactivators that include a folate residue, e.g., a compound of formula (I), wherein X 1 , X 2 , R 1 , and R 2 are as described herein. Also disclosed is a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier. Also disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells and inactivating AGT in a tumor cell. The methods comprise, inter alia, administering a compound or pharmaceutically acceptable salt of formula (I).

  本发明涉及一种包括叶酸残基的AGT失活剂化合物，例如式(I)的化合物，其中X1、X2、R1和R2如本文所述。本发明还涉及一种包括本发明化合物和药学上可接受的载体的制药组合物。本发明还涉及增强肿瘤细胞化疗治疗和失活肿瘤细胞中AGT的方法。该方法包括，除其他外，给予式(I)的化合物或药学上可接受的盐。
• Folic acid functionalization for targeting self-assembled paclitaxel-based nanoparticles
  作者：Eleonora Colombo、Davide Andrea Coppini、Simone Maculan、Pierfausto Seneci、Benedetta Santini、Filippo Testa、Lucia Salvioni、Giovanni Maria Vanacore、Miriam Colombo、Daniele Passarella

  DOI：10.1039/d2ra06306a

  日期：——

  Hetero-nanoparticles self-assembled from a conjugate bearing folic acid as the targeting agent, and another bearing paclitaxel as the active agent are reported. Hetero-nanoparticles containing varying percentages of folic acid conjugates are characterised, and their biological activity is determined.

  报道了由以叶酸为靶向剂的缀合物和另一种以紫杉醇为活性剂的缀合物自组装的杂纳米颗粒。表征了含有不同百分比的叶酸缀合物的杂纳米颗粒，并确定了它们的生物活性。
• Cryptophane-Folate Biosensor for ¹²⁹Xe NMR
  作者：Najat S. Khan、Brittany A. Riggle、Garry K. Seward、Yubin Bai、Ivan J. Dmochowski

  DOI：10.1021/bc5005526

  日期：2015.1.21

  Folate-conjugated cryptophane was developed for targeting cryptophane to membrane-bound folate receptors that are overexpressed in many human cancers. The cryptophane biosensor was synthesized in 20 nonlinear steps, which included functionalization with folate recognition moiety, solubilizing peptide, and Cy3 fluorophore. Hyperpolarized Xe-129 NMR studies confirmed xenon binding to the folate-conjugated cryptophane. Cellular internalization of biosensor was monitored by confocal laser scanning microscopy and quantified by flow cytometry. Competitive blocking studies confirmed cryptophane endocytosis through a folate receptor-mediated pathway. Flow cytometry revealed 10-fold higher cellular internalization in KB cancer cells overexpressing folate receptors compared to HT-1080 cells with normal folate receptor expression. The biosensor was determined to be nontoxic in HT-1080 and KB cells by MTT assay at low micromolar concentrations typically used for hyperpolarized Xe-129 NMR experiments.
• Development of an Efficient Intermediate, α-[2-(Trimethylsilyl)ethoxy]-2-<i>N</i>- [2-(trimethylsilyl)ethoxycarbonyl]folic Acid, for the Synthesis of Folate (γ)-Conjugates, and Its Application to the Synthesis of Folate−Nucleoside Conjugates
  作者：Makoto Nomura、Satoshi Shuto、Akira Matsuda

  DOI：10.1021/jo000132a

  日期：2000.8.1