2-[2-[2-[2-[2-[2-[2-(羧基甲氧基)乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙酸 | 83824-29-7

• 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
• 中文名称: 2-[2-[2-[2-[2-[2-[2-(羧基甲氧基)乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙酸
• 英文名称: 3,6,9,12,15,18,21-heptaoxatricosane-1,23-dioic acid
• 英文别名: 3,6,9,12,15,18,21-Heptaoxatricosanedioic acid；2-[2-[2-[2-[2-[2-[2-(carboxymethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetic acid
• CAS: 83824-29-7
• 化学式: C₁₆H₃₀O₁₁
• 分子量: 398.408
• InChiKey: RFYAZDYSJVSCDL-UHFFFAOYSA-N

物化性质

• 沸点：
  554.0±45.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  27
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  11

安全信息

• 储存条件：
  储存条件：2-8°C，干燥且密封。

制备方法与用途

CH2COOH-PEG6-CH2COOH 是一种PROTAC连接子，属于PEG类，可用于合成PROTAC分子。

反应信息

• 作为反应物：
  描述：

  2-[2-[2-[2-[2-[2-[2-(羧基甲氧基)乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-[2-[2-[2-[2-[2-[2-(2-chloro-2-oxoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl chloride
  参考文献：
  名称：

  Ligand Recognition by E- and P-Selectin:  Chemoenzymatic Synthesis and Inhibitory Activity of Bivalent Sialyl Lewis x Derivatives and Sialyl Lewis x Carboxylic Acids

  摘要：

  Described is the preparation of five sLe(x) dimers and five sLe(x) carboxylic acids by coupling chemoenzymatically synthesized amino-substituted sialyl Lewis x (sLe(x)) derivative 4 to homobifunctional cross-linkers 20-24 of varying chain length. 20-24 were obtained by alkylating low-molecular-weight oligoethylene glycols with tert-butyl bromoacetate and subsequent transformation of the di-tert-butyl esters into disuccinimide esters. The products were assayed for inhibition against binding of a sLe(a)-polymer to immobilized E- and P-selectin. In the E-selectin assay all dimers had lower IC50 values than the sLex monomer. The results show that comparable binding enhancements can be obtained with linkers of completely different length and rigidity. In the P-selectin assay four of the five sLe(x) carboxylic acids displayed significantly improved inhibitory potency. The lowest IC50 value was observed for the compound with the shortest spacer between the sLex moiety and the additional carboxylate, being ca. 20-40 times more potent than unmodified sLex. These findings should be of importance for the design of new multivalent forms of sLe(x) as well as sLe(x) mimetics as high-affinity selectin ligands.

  DOI：

  10.1021/jo980350s
• 作为产物：
  描述：

  六甘醇 在 lithium hydroxide monohydrate 、 三氟化硼乙醚 、 水 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 2-[2-[2-[2-[2-[2-[2-(羧基甲氧基)乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙氧基]乙酸
  参考文献：
  名称：

  WO2024059665A1

  摘要：

  公开号：

文献信息

• <i>N</i>-(7-Cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide (TAK632) Promotes Inhibition of BRAF through the Induction of Inhibited Dimers
  作者：Michael Grasso、Michelle A. Estrada、Kiara N. Berrios、Jeffrey D. Winkler、Ronen Marmorstein

  DOI：10.1021/acs.jmedchem.8b00499

  日期：2018.6.14

  stabilize an inactive αC-out/αC-out homodimeric conformation with improved inhibitor potency and selectivity in vitro. We set out to extend this strategy to target RAF homo- and heterodimers with the pan-RAF inhibitor TAK632 in dimeric configuration. Surprisingly, we find that monomeric TAK632 induces an active αC-in/αC-in BRAF dimer conformation, while dimeric TAK inhibitors cannot promote BRAF dimers

  BRAF V600E是黑色素瘤中最常见的激活突变，接受BRAF V600E抑制剂治疗的患者均在一年内产生耐药性。一个重要的抗性途径是涉及BRAF二聚体的反常激活（反式激活），由此抑制剂结合的蛋白亚基变构地激活其他亚基。我们最近报道了BRAF V600E二聚体选择性维罗非尼抑制剂，可稳定无活性的αC-out/αC-out同型二聚体构象，并在体外具有增强的抑制剂效价和选择性。我们着手将这一策略扩展为以二聚体构型的pan-RAF抑制剂TAK632靶向RAF同型和异二聚体。出乎意料的是，我们发现单体TAK632诱导了活跃的αC-in/αC-inBRAF二聚体构象，而二聚体TAK抑制剂则不能促进BRAF二聚体，并且在体外具有显着降低的效能。这些研究揭示了BRAF二聚化与TAK632抑制模式之间的密切联系，并强调了理解BRAF抑制剂对激酶二聚化影响的重要性。
• Solid phase synthesis of peptide dimers and trimers linked through an N-terminal lysine residue
  作者：M.Arfan Ashraf、Jatinder K. Notta、John S. Snaith

  DOI：10.1016/j.tetlet.2003.10.061

  日期：2003.12

  Peptide dimers and trimers linked through the epsilon-amino group of an N-terminal lysine residue can be prepared by cross linking peptide chains on the solid phase with a di- or trifunctional carboxylic acid, followed by cleavage from the resin. (C) 2003 Elsevier Ltd. All rights reserved.
• Ligand Recognition by E- and P-Selectin:  Chemoenzymatic Synthesis and Inhibitory Activity of Bivalent Sialyl Lewis x Derivatives and Sialyl Lewis x Carboxylic Acids
  作者：Valentin Wittmann、Shuichi Takayama、Ke Wei Gong、Gabriele Weitz-Schmidt、Chi-Huey Wong

  DOI：10.1021/jo980350s

  日期：1998.7.1

  Described is the preparation of five sLe(x) dimers and five sLe(x) carboxylic acids by coupling chemoenzymatically synthesized amino-substituted sialyl Lewis x (sLe(x)) derivative 4 to homobifunctional cross-linkers 20-24 of varying chain length. 20-24 were obtained by alkylating low-molecular-weight oligoethylene glycols with tert-butyl bromoacetate and subsequent transformation of the di-tert-butyl esters into disuccinimide esters. The products were assayed for inhibition against binding of a sLe(a)-polymer to immobilized E- and P-selectin. In the E-selectin assay all dimers had lower IC50 values than the sLex monomer. The results show that comparable binding enhancements can be obtained with linkers of completely different length and rigidity. In the P-selectin assay four of the five sLe(x) carboxylic acids displayed significantly improved inhibitory potency. The lowest IC50 value was observed for the compound with the shortest spacer between the sLex moiety and the additional carboxylate, being ca. 20-40 times more potent than unmodified sLex. These findings should be of importance for the design of new multivalent forms of sLe(x) as well as sLe(x) mimetics as high-affinity selectin ligands.
• WO2024059665A1
  申请人：——

  公开号：——

  公开（公告）日：——