ethyl 3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate | 1079251-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate
• 英文别名: ethyl 3-(3-naphthalen-1-yloxypropyl)-1H-indole-2-carboxylate
• CAS: 1079251-42-5
• 化学式: C₂₄H₂₃NO₃
• 分子量: 373.452
• InChiKey: STQFBPRAFIWSEO-UHFFFAOYSA-N

物化性质

• 沸点：
  596.4±45.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate 在 sodium hydride 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 16.33h， 生成 1-methyl-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design

  摘要：

  Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family of proteins, is overexpressed and amplified in various cancers and promotes the aberrant survival of tumor cells that otherwise would undergo apoptosis. Here we describe the discovery of potent and selective Mcl-1 inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified two chemically distinct hit series that bind to different sites on Mcl-1. Members of the two fragment classes were merged together to produce lead compounds that bind to Mcl-1 with a dissociation constant of <100 nM with selectivity for Mcl-1 over Bcl-xL and Bcl-2. Structures of merged compounds when complexed to Mcl-1 were obtained by X-ray crystallography and provide detailed information about the molecular recognition of small-molecule ligands binding Mcl-1. The compounds represent starting points for the discovery of clinically useful Mcl-1 inhibitors for the treatment of a wide variety of cancers.

  DOI：

  10.1021/jm301448p
• 作为产物：
  描述：

  6-ethoxy-6-oxo-5-(2-phenylhydrazono)hexanoic acid 在 硼烷四氢呋喃络合物 、 偶氮二甲酸二叔丁酯 、 硫酸 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 31.5h， 生成 ethyl 3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  [EN] SUBSTITUTED BENZOFURAN, BENZOTHIOPHENE AND INDOLE MCL-1 INHIBITORS
  [FR] INHIBITEURS DE LA MCL-1 À BASE DE BENZOFURANE, DE BENZOTHIOPHÈNE ET D'INDOLE SUBSTITUÉS

  摘要：

  公开号：

  WO2014047427A3

文献信息

• Structure-Guided Design of a Series of MCL-1 Inhibitors with High Affinity and Selectivity
  作者：Milan Bruncko、Le Wang、George S. Sheppard、Darren C. Phillips、Stephen K. Tahir、John Xue、Scott Erickson、Steve Fidanze、Elizabeth Fry、Lisa Hasvold、Gary J. Jenkins、Sha Jin、Russell A. Judge、Peter J. Kovar、David Madar、Paul Nimmer、Chang Park、Andrew M. Petros、Saul H. Rosenberg、Morey L. Smith、Xiaohong Song、Chaohong Sun、Zhi-Fu Tao、Xilu Wang、Yu Xiao、Haichao Zhang、Chris Tse、Joel D. Leverson、Steven W. Elmore、Andrew J. Souers

  DOI：10.1021/jm501258m

  日期：2015.3.12

  leukemia 1 (MCL-1) is a BCL-2 family protein that has been implicated in the progression and survival of multiple tumor types. Herein we report a series of MCL-1 inhibitors that emanated from a high throughput screening (HTS) hit and progressed via iterative cycles of structure-guided design. Advanced compounds from this series exhibited subnanomolar affinity for MCL-1 and excellent selectivity over other

  髓样细胞白血病1（MCL-1）是一种BCL-2家族蛋白，与多种肿瘤类型的进展和生存有关。在本文中，我们报告了一系列MCL-1抑制剂，这些抑制剂源于高通量筛选（HTS）命中并通过结构指导设计的迭代循环进行。该系列的先进化合物对MCL-1表现出亚纳摩尔亲和力，并且与其他BCL-2家族蛋白以及多种激酶和GPCR相比具有出色的选择性。在依赖MCL-1的人类肿瘤细胞系中，化合物30b的施用迅速诱导胱天蛋白酶激活，并伴有细胞活力的丧失。因此，本文所述的小分子包含用于研究MCL-1生物学的有效工具。
• 7-NONSUBSTITUTED INDOLE MCL-1 INHIBITORS
  申请人：Song Xiaohong

  公开号：US20090124616A1

  公开（公告）日：2009-05-14

  Compounds which inhibit the activity of anti-apoptotic Mcl-1 protein, compositions containing the compounds, and methods of treating diseases involving overexpressed or unregulated Mcl-1 protein are disclosed.

  本发明揭示了抑制抗凋亡蛋白Mcl-1活性的化合物、含有该化合物的组合物以及治疗涉及过度表达或调节Mcl-1蛋白的疾病的方法。
• SUBSTITUTED BENZOFURAN, BENZOTHIOPHENE AND INDOLE MCL-1 INHIBITORS
  申请人：VANDERBILT UNIVERSITY

  公开号：US20150336925A1

  公开（公告）日：2015-11-26

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了一种抑制抗凋亡Bcl-2家族成员髓系细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了制药组合物以及使用化合物治疗因Mcl-1蛋白过度表达或失调而表现出的疾病和症状（例如癌症）的方法。
• Substituted benzofuran, benzothiophene and indole MCL-1 inhibitors
  申请人：VANDERBILT UNIVERSITY

  公开号：US10093640B2

  公开（公告）日：2018-10-09

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了抑制抗凋亡 Bcl-2 家族成员骨髓细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了药物组合物以及使用化合物治疗以 Mcl-1 蛋白过度表达或失调为特征的疾病和病症（如癌症）的方法。
• Substituted benzofuran, benzothiophene and indole Mcl-1 inhibitors
  申请人：Vanderbilt University

  公开号：US10844032B2

  公开（公告）日：2020-11-24

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了抑制抗凋亡 Bcl-2 家族成员骨髓细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了药物组合物以及使用化合物治疗以 Mcl-1 蛋白过度表达或失调为特征的疾病和病症（如癌症）的方法。