methyl 4-(2-bromobenzamido)benzoate | 304664-13-9

• 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: methyl 4-(2-bromobenzamido)benzoate
• 英文别名: Methyl 4-[(2-bromobenzoyl)amino]benzoate
• CAS: 304664-13-9
• 化学式: C₁₅H₁₂BrNO₃
• mdl: MFCD00423312
• 分子量: 334.169
• InChiKey: IKJQHRCSOBEEBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(2-bromobenzamido)benzoate 在 palladium diacetate 、 sodium hydride 、 caesium carbonate 、 tricyclohexylphosphine tetrafluoroborate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 methyl 5-methyl-6-oxo-5,6-dihydrophenanthridine-2-carboxylate
  参考文献：
  名称：

  Phenanthridin-6-one derivatives as the first class of non-steroidal pharmacological chaperones for Niemann-Pick disease type C1 protein

  摘要：

  Niemann-Pick disease type C is a fatal, progressive neurodegenerative disease mostly caused by mutations in Nieamnn-Pick type C1 (NPC1), a late endosomal membrane protein that is essential for intracellular cholesterol transport. The most prevalent mutation, I1061T (Ile to Thr), interferes with the protein folding process. Consequently, mutated but intrinsically functional NPC1 proteins are prematurely degraded via proteasome, leading to loss of NPC1 function. Previously, we reported sterol derivatives as pharmacological chaperones for NPC1, and showed that these derivatives can normalize folding-defective phenotypes of I1061T NPC1 mutant by directly binding to, and stabilizing, the protein. Here, we report a series of compounds containing a phenanthridin-6-one scaffold as the first class of non-steroidal pharmacological chaperones for NPC1. We also examined their structure-activity relationships. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.062
• 作为产物：
  描述：

  2-溴苯甲酰氯 、 4-氨基苯甲酸甲酯 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 9.0h， 以88%的产率得到methyl 4-(2-bromobenzamido)benzoate
  参考文献：
  名称：

  非甾体NPC1L1配体的结构-活性关系研究，通过基于细胞的分析以药理伴侣效应作为读数进行鉴定

  摘要：

  Niemann-Pick C1样1（NPC1L1）是一种肠道胆固醇转运蛋白，已知是胆固醇吸收抑制剂依泽替米贝的靶标。我们以前通过使用一种新的基于细胞的测定法发现了甾体NPC1L1配体，该测定法采用药理分子伴侣效应作为读数。这些类固醇衍生物与不同于固醇结合域和依泽麦布结合位点的位点结合，这意味着它们可能是一类具有独特作用方式的新型NPC1L1抑制剂。作为这项工作的延伸，我们的目标是通过使用相同的分析方法筛选聚焦于肝X受体（LXR）的配体库，从而找到非甾体NPC1L1配体，这些配体可能比甾体配体更适合临床应用。将氧固醇识别为内源性配体的核受体。

  DOI：

  10.1016/j.bmc.2014.05.022

文献信息

• [EN] DYNAMIN-1-LIKE PROTEIN INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINE DE TYPE DYNAMINE-1
  申请人：MITOBRIDGE INC

  公开号：WO2018200674A1

  公开（公告）日：2018-11-01

  This application is directed to inhibitors of dynamin-l-like protein (Drpl) represented by the following structural formula (I): and methods for their use, such as to treat one or more DRPl-related diseases.

  该申请涉及以下结构公式（I）表示的dynamin-l样蛋白（Drpl）的抑制剂：以及它们的使用方法，例如用于治疗一种或多种与DRPl相关的疾病。
• Dynamin-1-like protein inhibitors
  申请人：Mitobridge, Inc.

  公开号：US11168080B2

  公开（公告）日：2021-11-09

  This application is directed to inhibitors of dynamin-1-like protein (Drp1) represented by the following structural formula (I): and methods for their use, such as to treat one or more DRP1-related diseases.

  本申请涉及以下列结构式（I）为代表的Dynamin-1样蛋白（Drp1）抑制剂及其使用方法，例如治疗一种或多种DRP1相关疾病。
• Synthesis of 3-Substituted and 2,3-Disubstituted Quinazolinones via Cu-Catalyzed Aryl Amidation
  作者：Lanting Xu、Yongwen Jiang、Dawei Ma

  DOI：10.1021/ol300084v

  日期：2012.2.17

  Cul/4-hydroxy-L-proline catalyzed coupling of N-substituted o-bromobenzamides with formamide takes place at 80 degrees C, affording 3-substituted quinazolinones directly. Under these conditions other amides that were tested only provided simple coupling products, which can be converted into 2,3-disubstituted quinazolinones via HMDS/ZnCl2 mediated condensative cyclization.
• DYNAMIN-1-LIKE PROTEIN INHIBITORS
  申请人：Mitobridge, Inc.

  公开号：US20200131172A1

  公开（公告）日：2020-04-30

  This application is directed to inhibitors of dynamin-1-like protein (Drp1) represented by the following structural formula (I): and methods for their use, such as to treat one or more DRP1-related diseases.
• Structure–activity relationship study of non-steroidal NPC1L1 ligands identified through cell-based assay using pharmacological chaperone effect as a readout
  作者：Fumika Karaki、Kenji Ohgane、Hiromitsu Fukuda、Masahiko Nakamura、Kosuke Dodo、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2014.05.022

  日期：2014.7

  We previously discovered steroidal NPC1L1 ligands by using a novel cell-based assay that employs pharmacological chaperone effect as a readout. Those steroid derivatives bound to a site different from both the sterol-binding domain and the ezetimibe-binding site, implying that they may be a novel class of NPC1L1 inhibitors with a distinct mode of action. As an extension of that work, we aimed here

  Niemann-Pick C1样1（NPC1L1）是一种肠道胆固醇转运蛋白，已知是胆固醇吸收抑制剂依泽替米贝的靶标。我们以前通过使用一种新的基于细胞的测定法发现了甾体NPC1L1配体，该测定法采用药理分子伴侣效应作为读数。这些类固醇衍生物与不同于固醇结合域和依泽麦布结合位点的位点结合，这意味着它们可能是一类具有独特作用方式的新型NPC1L1抑制剂。作为这项工作的延伸，我们的目标是通过使用相同的分析方法筛选聚焦于肝X受体（LXR）的配体库，从而找到非甾体NPC1L1配体，这些配体可能比甾体配体更适合临床应用。将氧固醇识别为内源性配体的核受体。