3-oxo-1-phenyl-2,5,8,11-tetraoxatridecan-13-oic acid | 146773-32-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-oxo-1-phenyl-2,5,8,11-tetraoxatridecan-13-oic acid
• 英文别名: 2-[2-[2-(2-benzyloxy-2-oxo-ethoxy)ethoxy]ethoxy]acetic acid；2-[2-[2-(2-Oxo-2-phenylmethoxyethoxy)ethoxy]ethoxy]acetic acid
• CAS: 146773-32-2
• 化学式: C₁₅H₂₀O₇
• 分子量: 312.32
• InChiKey: VLAOBLJYPLUGKH-UHFFFAOYSA-N

物化性质

• 沸点：
  474.8±35.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-oxo-1-phenyl-2,5,8,11-tetraoxatridecan-13-oic acid 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(2-(2-(2-((4-((2-((tert-butoxycarbonyl)amino)-4-fluorophenyl)carbamoyl)phenyl)amino)-2-oxoethoxy)ethoxy)ethoxy)acetic acid
  参考文献：
  名称：

  I 类组蛋白脱乙酰酶 PROTAC 的优化表明 HDAC1/2 降解对于诱导癌细胞凋亡和细胞停滞至关重要

  摘要：

  I 类组蛋白脱乙酰酶 (HDAC) 酶 1、2 和 3 将染色质组织为七种不同的多蛋白辅阻遏物复合物中的催化亚基，并且是既定的药物靶标。我们报告了基于苯甲酰胺的 Von Hippel–Lindau (VHL) E3 连接酶蛋白水解靶向嵌合体 (PROTAC) 的优化研究，并首次描述了由这些降解剂引起的转录组扰动。通过修饰接头和 VHL 配体，我们鉴定了具有亚微摩尔 DC 50的 PROTAC 7、9和22HCT116 细胞中 HDAC1 和/或 HDAC3 的值。观察到 HDAC3 的钩状效应，可以通过修改 VHL 配体与接头的连接位置来消除这种效应。更有效的 HDAC1/2 降解剂与更大的总差异表达基因和增强的 HCT116 细胞凋亡相关。我们证明 PROTAC 对 HDAC1/2 的降解与增强的全局基因表达和细胞凋亡相关，这对于开发更有效且副作用更少的 HDAC 疗法非常重要。

  DOI：

  10.1021/acs.jmedchem.1c02179
• 作为产物：
  描述：

  3,6,9-trioxaundecane-1,11-dioic acid anhydride 、 苯甲醇 在 三氟乙酸 作用下， 反应 12.0h， 生成 3-oxo-1-phenyl-2,5,8,11-tetraoxatridecan-13-oic acid
  参考文献：
  名称：

  WO2008/75192

  摘要：

  公开号：

文献信息

• [EN] COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS
  申请人：FOGHORN THERAPEUTICS INC

  公开号：WO2021207291A1

  公开（公告）日：2021-10-14

  The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

  本公开内容涉及用于治疗BAF复合物相关疾病的化合物。
• [EN] COMPOUNDS AND METHODS OF TREATING CANCERS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE CANCERS
  申请人：CULLGEN SHANGHAI INC

  公开号：WO2020200291A1

  公开（公告）日：2020-10-08

  This disclosure relates to heterobifunctional compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the heterobifunctional compounds, and to methods of use the heterobifunctional compounds for the treatment of certain disease in a subject in need thereof. The disclosure also relates to methods for identifying such heterobifunctional compounds.

  这份披露涉及异双功能化合物（例如，双功能小分子化合物），包括一种或多种异双功能化合物的组合物，以及使用这些异双功能化合物治疗患有特定疾病的需要该类治疗的受试者的方法。该披露还涉及识别此类异双功能化合物的方法。
• [EN] CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN (CBP) AND/OR ADENOVIRAL E1A BINDING PROTEIN OF 300 KDA (P300) DEGRADATION COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS DE DÉGRADATION DE PROTÉINE DE LIAISON À L'ÉLÉMENT DE RÉPONSE D'AMP CYCLIQUE (CBP) ET/OU PROTÉINE DE LIAISON E1A ADÉNOVIRALE DE 300 KDA (P300) ET MÉTHODES D'UTILISATION
  申请人：CULLGEN SHANGHAI INC

  公开号：WO2022042707A1

  公开（公告）日：2022-03-03

  Provided are bivalent compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the bivalent compounds, and methods of use the bivalent compounds for the treatment of certain disease in a subject in need thereof, and methods for identifying such bivalent compounds.

  提供双价化合物（例如，双官能团小分子化合物），包含一种或多种双价化合物的组合物，以及使用双价化合物治疗需要的患者某些疾病的方法，以及鉴定此类双价化合物的方法。
• Novel tumor-targeted RGD peptide–camptothecin conjugates: Synthesis and biological evaluation
  作者：Alma Dal Pozzo、Ming-Hong Ni、Emiliano Esposito、Sabrina Dallavalle、Loana Musso、Alberto Bargiotti、Claudio Pisano、Loredana Vesci、Federica Bucci、Massimo Castorina、Rosanna Foderà、Giuseppe Giannini、Concetta Aulicino、Sergio Penco

  DOI：10.1016/j.bmc.2009.11.019

  日期：2010.1

  Five RGD peptide-camptothecin (CPT) conjugates were designed and synthesized with the purpose to improve the therapeutic index of this antitumoral drug family. New RGD cyclopeptides were selected on the basis of their high affinity to alpha(v) integrin receptors overexpressed by tumor cells and their metabolic stability. The conjugates can be divided in two groups: in the first the peptide was attached to the drug through an amide bond, in the second through a hydrazone bond. The main difference between the two spacers lies in their acid stability. Affinity to the receptors was maintained for all conjugates and their internalization into tumor cells was demonstrated. The first group conjugates showed lower in vitro and in vivo activity than the parent drug, probably due to the excessive stability of the amide bond, even inside the tumor cells. Conversely, the hydrazone conjugates exhibited in vitro tumor cell inhibition similar to the parent drug, indicating high conversion in the culture medium and/or inside the cells, but their poor solubility hampered in vivo experiments. On the basis of these results, information was acquired for additional development of derivatives with different linkers and better solubility for in vivo evaluation. (C) 2009 Elsevier Ltd. All rights reserved.
• NG-Acyl-argininamides as NPY Y1 receptor antagonists: Influence of structurally diverse acyl substituents on stability and affinity
  作者：Stefan Weiss、Max Keller、Günther Bernhardt、Armin Buschauer、Burkhard König

  DOI：10.1016/j.bmc.2010.07.028

  日期：2010.9

  N-G-Acylated argininamides, covering a broad range of lipophilicity (calculated log D values: -1.8-12.5), were synthesized and investigated for NPY Y-1 receptor (Y1R) antagonism, Y1R affinity and stability in buffer (N-G-deacylation, yielding BIBP 3226). Broad structural variation of substituents was tolerated. The K-i (binding) and K-b values (Y1R antagonism) varied from low nM to one-digit mu M. Most of the compounds proved to be sufficiently stable at pH 7.4 over 90 min to determine reliable pharmacological data in vitro. Exceptionally high instability was detected when a succinyl moiety was attached to the guanidine, probably, due to an intramolecular cleavage mechanism. (C) 2010 Elsevier Ltd. All rights reserved.