methyl 3-(3-((tert-butoxycarbonyl)amino)prop-1-yn-1-yl)-6-hydroxy-1-methyl-2-(2-(trifluoromethyl) phenyl)-1H-indole-5-carboxylate | 1404436-76-5

• 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: methyl 3-(3-((tert-butoxycarbonyl)amino)prop-1-yn-1-yl)-6-hydroxy-1-methyl-2-(2-(trifluoromethyl) phenyl)-1H-indole-5-carboxylate
• 英文别名: methyl 3-(3-((tert-butoxycarbonyl)amino)prop-1-yn-1-yl)-6-hydroxy-1methyl-2-(2-(trifluoromethyl) phenyl)-1H-indole-5-carboxylate；Methyl 3-(3-((tert-butoxycarbonyl)amino)prop-1-yn-1-yl)-6-hydroxy-1-methyl-2-(2-(trifluoromethyl) phenyl)-1H-indole-5-carboxylate；methyl 6-hydroxy-1-methyl-3-[3-[(2-methylpropan-2-yl)oxycarbonylamino]prop-1-ynyl]-2-[2-(trifluoromethyl)phenyl]indole-5-carboxylate
• CAS: 1404436-76-5
• 化学式: C₂₆H₂₅F₃N₂O₅
• 分子量: 502.49
• InChiKey: RUMQKBZMQDMDQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 3-(3-((tert-butoxycarbonyl)amino)prop-1-yn-1-yl)-6-hydroxy-1-methyl-2-(2-(trifluoromethyl) phenyl)-1H-indole-5-carboxylate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 3-(3-aminopropanoyl)-6-hydroxy-1-methyl-2-(2-(trifluoromethyl)phenyl)-1H-indole-5-carboxylic acid
  参考文献：
  名称：

  一种简便的基于羟基吲哚羧酸的聚焦库方法，用于分枝杆菌蛋白酪氨酸磷酸酶 B 的强效和选择性抑制剂

  摘要：

  专注于 Mtb：设计了一种基于羟基吲哚羧酸的简便的聚焦酰胺库，旨在同时靶向 PTP 活性位点和独特的附近口袋，以提高亲和力和选择性。文库的 HTS 导致鉴定了mPTPB的高效选择性抑制剂11a，mPTPB 是结核分枝杆菌的重要毒力因子。化合物11a显示出高细胞活性并且能够逆转巨噬细胞中由 mPTPB 诱导的改变的免疫反应。

  DOI：

  10.1002/cmdc.201300115
• 作为产物：
  描述：

  p-(dimethylamino)salicylic acid methyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 碘 、 potassium carbonate 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl 3-(3-((tert-butoxycarbonyl)amino)prop-1-yn-1-yl)-6-hydroxy-1-methyl-2-(2-(trifluoromethyl) phenyl)-1H-indole-5-carboxylate
  参考文献：
  名称：

  一种简便的基于羟基吲哚羧酸的聚焦库方法，用于分枝杆菌蛋白酪氨酸磷酸酶 B 的强效和选择性抑制剂

  摘要：

  专注于 Mtb：设计了一种基于羟基吲哚羧酸的简便的聚焦酰胺库，旨在同时靶向 PTP 活性位点和独特的附近口袋，以提高亲和力和选择性。文库的 HTS 导致鉴定了mPTPB的高效选择性抑制剂11a，mPTPB 是结核分枝杆菌的重要毒力因子。化合物11a显示出高细胞活性并且能够逆转巨噬细胞中由 mPTPB 诱导的改变的免疫反应。

  DOI：

  10.1002/cmdc.201300115

文献信息

• [EN] TYROSINE PHOSPHATASE INHIBITORS AND USES THEREOF TO MODULATE THE ACTIVITY OF LYP<br/>[FR] INHIBITEURS DE LA TYROSINE PHOSPHATASE ET LEURS UTILISATIONS POUR MODULER L'ACTIVITÉ DE LA PROTÉINE LYP
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2012149048A1

  公开（公告）日：2012-11-01

  A variety of benzofurans and indole derivatives some with an acetyl linker are disclosed herein. These compounds are not highly charged at physiological pH and have good bioavailability characteristics. These compounds exhibit selective or at least preferential affinity for the active sites of various sub-sets of protein tyrosine phosphatases. The lymphoid- specific tyrosine phosphatase (Lyp) has received enormous attention because of the finding that a single- nucleotide polymorphism (SNP) in the gene (PTPN22) encoding Lyp is associated with several autoimmune diseases, including type I diabetes. Many of these compounds and pharmaceutically acceptable salts thereof are novel therapeutic compounds useful for the treatment of various diseases including a number of autoimmune diseases.

  本文披露了一系列苯并呋喃和吲哚衍生物，其中一些带有乙酰连接物。这些化合物在生理pH下不具有高电荷，并具有良好的生物利用度特性。这些化合物表现出对各种亚型蛋白酪氨酸磷酸酶的活性位点具有选择性或至少具有偏好亲和性。淋巴细胞特异性酪氨酸磷酸酶(Lyp)因发现编码Lyp的基因(PTPN22)中的单核苷酸多态性(SNP)与多种自身免疫疾病，包括I型糖尿病有关，因此受到了巨大关注。这些化合物中的许多及其药用盐是新颖的治疗化合物，可用于治疗包括多种自身免疫疾病在内的各种疾病。
• TYROSINE PHOSPHATASE INHIBITORS AND USES THEREOF TO MODULATE THE ACTIVITY OF ENZYMESp INVOLVED IN THE PATHOLOGY OF MYCOBACTERIUM TUBERCULOSIS
  申请人：Zhang Zhong-Yin

  公开号：US20140179735A1

  公开（公告）日：2014-06-26

  A variety of benzofurans and indole derivatives some with an alkynyl linker are disclosed herein. These compounds are not highly charged at physiological pH and have good bioavailability characteristics. These compounds exhibit selective or at least preferential affinity for the active sites of various sub-sets of protein tyrosine phosphatases. Some of these compounds are excellent inhibitors of Mycobacterium protein tyrosine phosphatase B (mPTPB) a protein tyrosine phosphatase expressed in Mycobacterium tuberculosis and characterized as a virulence factor in the causal agent of tuberculosis. Accordingly, many of these compounds and pharmaceutically acceptable salts thereof are useful for the treatment of diseases such as tuberculosis.

  本文介绍了一系列苯并呋喃和吲哚衍生物，其中一些具有炔基连接物。这些化合物在生理pH值下电荷不高，具有良好的生物利用度特性。这些化合物表现出对各种亚集蛋白酪氨酸磷酸酶的活性位点具有选择性或至少具有优先亲和性。其中一些化合物是良好的Mycobacterium蛋白酪氨酸磷酸酶B（mPTPB）的抑制剂，这是一种在结核病的病原体Mycobacterium tuberculosis中表达的蛋白酪氨酸磷酸酶，并被认为是一种毒力因子。因此，这些化合物和其药学上可接受的盐对于治疗结核病等疾病非常有用。
• US9493436B2
  申请人：——

  公开号：US9493436B2

  公开（公告）日：2016-11-15
• [EN] TYROSINE PHOSPHATASE INHIBITORS AND USES THEREOF TO MODULATE THE ACTIVITY OF ENZYMES INVOLVED IN THE PATHOLOGY OF MYCOBACTERIUM TUBERCULOSIS<br/>[FR] INHIBITEURS DE LA TYROSINE PHOSPHATASE ET LEURS UTILISATIONS POUR MODULER L'ACTIVITÉ DES ENZYMES IMPLIQUÉES DANS LA PATHOLOGIE DE MYCOBACTERIUM TUBERCULOSIS
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2012149049A1

  公开（公告）日：2012-11-01

  A variety of benzofurans and indole derivatives some with an alkynyl linker are disclosed herein. These compounds are not highly charged at physiological pH and have good bioavailability characteristics. These compounds exhibit selective or at least preferential affinity for the active sites of various sub-sets of protein tyrosine phosphatases. Some of these compounds are excellent inhibitors of Mycobacterium protein tyrosine phosphatase B (mPTPB) a protein tyrosine phosphatase expressed in Mycobacterium tuberculosis and characterized as a virulence factor in the causal agent of tuberculosis. Accordingly, many of these compounds and pharmaceutically acceptable salts thereof are useful for the treatment of diseases such as tuberculosis.
• A Facile Hydroxyindole Carboxylic Acid Based Focused Library Approach for Potent and Selective Inhibitors of<i>Mycobacterium</i>Protein Tyrosine Phosphatase B
  作者：Li-Fan Zeng、Jie Xu、Yantao He、Rongjun He、Li Wu、Andrea M. Gunawan、Zhong-Yin Zhang

  DOI：10.1002/cmdc.201300115

  日期：2013.6

  Focused on Mtb: A facile hydroxyindole carboxylic acid based focused amide library was designed to target both the PTP active site and a unique nearby pocket for enhanced affinity and selectivity. HTS of the library led to the identification of a highly potent and selective inhibitor, 11 a, of mPTPB, an essential virulence factor for Mycobacterium tuberculosis. Compound 11 a shows high cellular activity

  专注于 Mtb：设计了一种基于羟基吲哚羧酸的简便的聚焦酰胺库，旨在同时靶向 PTP 活性位点和独特的附近口袋，以提高亲和力和选择性。文库的 HTS 导致鉴定了mPTPB的高效选择性抑制剂11a，mPTPB 是结核分枝杆菌的重要毒力因子。化合物11a显示出高细胞活性并且能够逆转巨噬细胞中由 mPTPB 诱导的改变的免疫反应。