3-[3-[2-(trifluoromethyl)phenoxy]propyl]-1H-indole-2-carboxylic acid | 1415968-27-2

• 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: 3-[3-[2-(trifluoromethyl)phenoxy]propyl]-1H-indole-2-carboxylic acid
• CAS: 1415968-27-2
• 化学式: C₁₉H₁₆F₃NO₃
• 分子量: 363.336
• InChiKey: ZYUVAKAGNDFDQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate 在 偶氮二甲酸二叔丁酯 、 三苯基膦 、 sodium hydroxide 、 diborane(6) 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 45.0h， 生成 3-[3-[2-(trifluoromethyl)phenoxy]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

文献信息

• Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design
  作者：Anders Friberg、Dominico Vigil、Bin Zhao、R. Nathan Daniels、Jason P. Burke、Pedro M. Garcia-Barrantes、DeMarco Camper、Brian A. Chauder、Taekyu Lee、Edward T. Olejniczak、Stephen W. Fesik

  DOI：10.1021/jm301448p

  日期：2013.1.10

  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.