methyl 4-[1-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl]-5-chloroindol-2-yl]butanoate | 927961-95-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: methyl 4-[1-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl]-5-chloroindol-2-yl]butanoate
• 英文别名: 1-[(2-amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-indole-2-butanoic acid methyl ester；Methyl 4-[1-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl]-5-chloroindol-2-yl]butanoate
• CAS: 927961-95-3
• 化学式: C₂₀H₁₈ClN₃O₄S₂
• 分子量: 463.966
• InChiKey: NLDMWZJOXMWYMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-[1-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl]-5-chloroindol-2-yl]butanoate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以49%的产率得到4-[1-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl]-5-chloroindol-2-yl]butanoic acid
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate

  摘要：

  Here, we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPAR alpha activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology suggesting therapeutic potential for NASH patients.

  DOI：

  10.1021/acs.jmedchem.7b01285
• 作为产物：
  描述：

  4-氯-2-碘硝基苯 在 吡啶 、 copper(l) iodide 、 四(三苯基膦)钯 、 乙醇 、 copper diacetate 、 三乙胺 、 tin(ll) chloride 作用下， 以 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.5h， 生成 methyl 4-[1-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl]-5-chloroindol-2-yl]butanoate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate

  摘要：

  Here, we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPAR alpha activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology suggesting therapeutic potential for NASH patients.

  DOI：

  10.1021/acs.jmedchem.7b01285

文献信息

• Indole Compounds, Method of Preparing Them and Uses Thereof
  申请人：BINET Jean

  公开号：US20080153816A1

  公开（公告）日：2008-06-26

  Indole compounds corresponding to the formula (I): as defined in the claims, pharmaceutically acceptable addition salts of such compounds, pharmaceutical compositions containing such compounds, the process for their preparation, and their use as pharmacologically active substances, especially in the treatment of hypertriglyceridemia, hyperlipidemia, hypercholesterolemia, diabetes, endothelial dysfunction, cardiovascular disease, inflammatory disease and neurodegeneration.

  与公式（I）相对应的吲哚化合物，如权利要求中所定义的，这些化合物的药学上可接受的加盐物，含有这些化合物的药物组合物，其制备方法，以及它们作为药理活性物质的用途，特别是在治疗高三酰甘油血症、高脂血症、高胆固醇血症、糖尿病、内皮功能障碍、心血管疾病、炎症性疾病和神经退行性疾病方面。
• Method of Treating Conditions Involving PPAR-Receptors with Indole Compounds
  申请人：BINET Jean

  公开号：US20100286137A1

  公开（公告）日：2010-11-11

  Indole compounds corresponding to the formula (I): as defined in the claims, pharmaceutically acceptable addition salts of such compounds, pharmaceutical compositions containing such compounds, the process for their preparation, and their use as pharmacologically active substances, especially in the treatment of hypertriglyceridemia, hyperlipidemia, hypercholesterolemia, diabetes, endothelial dysfunction, cardiovascular disease, inflammatory disease and neurodegeneration.

  本发明涉及化合物的吲哚类似物(I)的配方，这些化合物的药学上可接受的加盐物，含有这些化合物的制药组合物，其制备过程，以及作为药理活性物质的用途，特别是在高甘油三酯血症，高脂血症，高胆固醇血症，糖尿病，内皮功能障碍，心血管疾病，炎症性疾病和神经退行性疾病的治疗中。
• US7795297B2
  申请人：——

  公开号：US7795297B2

  公开（公告）日：2010-09-14
• US8436040B2
  申请人：——

  公开号：US8436040B2

  公开（公告）日：2013-05-07
• Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate
  作者：Benaïssa Boubia、Olivia Poupardin、Martine Barth、Jean Binet、Philippe Peralba、Laurent Mounier、Elise Jacquier、Emilie Gauthier、Valérie Lepais、Maryline Chatar、Stéphanie Ferry、Anne Thourigny、Fabrice Guillier、Jonathan Llacer、Jérome Amaudrut、Pierre Dodey、Olivier Lacombe、Philippe Masson、Christian Montalbetti、Guillaume Wettstein、Jean-Michel Luccarini、Christiane Legendre、Jean-Louis Junien、Pierre Broqua

  DOI：10.1021/acs.jmedchem.7b01285

  日期：2018.3.22

  Here, we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPAR alpha activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology suggesting therapeutic potential for NASH patients.