3-[5-[(Z)-(3-oxobenzothiophen-2-ylidene)methyl]-2-furyl]benzoic acid

• 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-[5-[(Z)-(3-oxobenzothiophen-2-ylidene)methyl]-2-furyl]benzoic acid
• 英文别名: 3-[5-[(Z)-(3-oxo-1-benzothiophen-2-ylidene)methyl]furan-2-yl]benzoic acid
• 化学式: C₂₀H₁₂O₄S
• 分子量: 348.379
• InChiKey: CGUMWJHNQHUQLW-WQRHYEAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[5-[(Z)-(3-oxobenzothiophen-2-ylidene)methyl]-2-furyl]benzoic acid 、 异丙胺 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以63%的产率得到(Z)-N-isopropyl-3-(5-((3-oxobenzo[b]thiophen-2(3H)-ylidene)methyl)furan-2-yl)benzamide
  参考文献：
  名称：

  发现针对白血病细胞中致癌酪氨酸磷酸酶 SHP2 的新型呋喃苯甲酰胺抑制剂。

  摘要：

  众所周知，由蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶 (PTP) 控制的信号分子酪氨酸磷酸化和去磷酸化之间的动态平衡的紊乱会导致癌症的发生。虽然大多数批准的靶向癌症疗法是酪氨酸激酶抑制剂，但 PTP 长期以来一直被认为是不可成药的，直到最近才在药物发现领域重新受到关注。 PTP 靶标之一是包含 Src-homology 2 结构域的磷酸酶 2 (SHP2)。 SHP2 与肿瘤发生、进展、转移和治疗耐药有关，主要是因为它作为细胞外信号调节激酶途径的信号连接，作用于小 GTPase Ras 的上游。开发针对 SHP2 的小分子的努力正在进行中，并且几种 SHP2 变构抑制剂目前正在进行治疗实体瘤的临床试验。然而，虽然报道的变构抑制剂对表达 WT SHP2 的细胞非常有效，但没有一种变构抑制剂对最常见的致癌 SHP2 变体具有显着活性，这些变体在几种青少年和急性白血病中驱动白血病发生。在这里，我们报告了新型呋喃苯甲酰胺分子作为

  DOI：

  10.1016/j.jbc.2021.101477

文献信息

• SMALL MOLECULES FOR THE MODULATION OF MCL-1 AND METHODS OF MODULATING CELL DEATH, CELL DIVISION, CELL DIFFERENTIATION AND METHODS OF TREATING DISORDERS
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP3138838A1

  公开（公告）日：2017-03-08

  This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.

  本发明涉及以高亲和力和选择性与存活蛋白 MCL-1 选择性结合的化合物、含有此类化合物的药物组合物，以及使用这些化合物或组合物调节 MCL-1 活性和治疗过度增殖性疾病、血管生成疾病、细胞周期调节疾病、自噬调节疾病、炎症性疾病和/或感染性疾病和/或增强细胞移植和/或伤口修复，可作为单独制剂或与其他活性成分组合使用。
• Small molecules for the modulation of MCL-1 and methods of modulating cell death, cell division, cell differentiation and methods of treating disorders
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10000511B2

  公开（公告）日：2018-06-19

  This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.

  本发明涉及以高亲和力和选择性与存活蛋白 MCL-1 选择性结合的化合物、含有此类化合物的药物组合物，以及使用这些化合物或组合物调节 MCL-1 活性和治疗过度增殖性疾病、血管生成疾病、细胞周期调节疾病、自噬调节疾病、炎症性疾病和/或感染性疾病和/或增强细胞移植和/或伤口修复，可作为单独制剂或与其他活性成分组合使用。
• Chemical entities that kill senescent cells for use in treating age-related disease
  申请人：Unity Biotechnology, Inc.

  公开号：US10195213B2

  公开（公告）日：2019-02-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.

  本文公开的化合物可有效治疗与衰老有关的各种疾病状态。所公开的化合物可用于消除衰老细胞以治疗疾病。化合物的给药方式包括单次给药和循环给药。
• COMPOUNDS WITH HIV-1 INTEGRASE INHIBITORY ACTIVITY AND USE THEREOF AS ANTI-HIV/AIDS THERAPEUTICS
  申请人：Neamati Nouri

  公开号：US20090088420A1

  公开（公告）日：2009-04-02

  Pharmacophore models to be used in drug design and discovery are provided. An in silico protocol and in vitro assays are presented. Compounds and their pharmaceutically acceptable salts with HIV-1 integrase inhibitory and anti-HIV activity and use thereof in the treatment of HIV/AIDS and related infections either alone or in combination with all the known antiretroviral therapeutics are described.
• COMPOUNDS AND THERAPEUTIC USES
  申请人：Unity Biotechnology, Inc.

  公开号：US20170281649A1

  公开（公告）日：2017-10-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.