tert-butyl 5-carbamothioyl-1H-indole-1-carboxylate

• 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: tert-butyl 5-carbamothioyl-1H-indole-1-carboxylate
• 英文别名: 5-Thiocarbamoyl-indole-1-carboxylic acid tert-butyl ester；tert-butyl 5-carbamothioylindole-1-carboxylate
• 化学式: C₁₄H₁₆N₂O₂S
• 分子量: 276.359
• InChiKey: ULRSEMCBTLFFDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  89.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-carbamothioyl-1H-indole-1-carboxylate 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 12.5h， 生成 1-(5-(4-((dimethylamino)methyl)thiazol-2-yl)-1H-indol-3-yl)-2,2,2-trifluoroethan-1-one
  参考文献：
  名称：

  Discovery of Novel Indole-Based Allosteric Highly Potent ATX Inhibitors with Great In Vivo Efficacy in a Mouse Lung Fibrosis Model

  摘要：

  Autotaxin (ATX) is the dominant catalytic enzyme accounting for the lipid mediator lysophosphatidic acid (LPA) through hydrolysis of lysophosphatidylcholine (LPC). There is great interest in developing nonacidic ATX inhibitors with a specific binding mode to serve as potential in vivo effective therapeutic tools. Herein, dating from a high-throughput screening (HTS) product Indole-1 (740 nM), a dedicated optimization campaign was implemented through derivatizing the -COOH group to versatile linkers that well-bridged the indole skeleton and the hydrophobic pocket binding groups. Ultimately, it was established that the coexistence of a carbamate linker and -OH-group-containing amines could generally furnish excellent indole-based ATX inhibitors with even below 1 nM in vitro activities. Two optimal entities were advanced to a bleomycin-induced mice pulmonary fibrosis model, which exerted promising efficacy in alleviating the damaged lung texture caused by bleomycin exposure. The novel carbamate-containing indole-based ATX inhibitors with a concrete binding mode may contribute to the identification of potential therapeutic agents to intervene in fibrotic diseases.

  DOI：

  10.1021/acs.jmedchem.0c00506
• 作为产物：
  描述：

  1-BOC-5-氰基吲哚 在 sodium hydrogen sulfide 、 magnesium(II) chloride hexahydrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以77.3%的产率得到tert-butyl 5-carbamothioyl-1H-indole-1-carboxylate
  参考文献：
  名称：

  Discovery of Novel Indole-Based Allosteric Highly Potent ATX Inhibitors with Great In Vivo Efficacy in a Mouse Lung Fibrosis Model

  摘要：

  Autotaxin (ATX) is the dominant catalytic enzyme accounting for the lipid mediator lysophosphatidic acid (LPA) through hydrolysis of lysophosphatidylcholine (LPC). There is great interest in developing nonacidic ATX inhibitors with a specific binding mode to serve as potential in vivo effective therapeutic tools. Herein, dating from a high-throughput screening (HTS) product Indole-1 (740 nM), a dedicated optimization campaign was implemented through derivatizing the -COOH group to versatile linkers that well-bridged the indole skeleton and the hydrophobic pocket binding groups. Ultimately, it was established that the coexistence of a carbamate linker and -OH-group-containing amines could generally furnish excellent indole-based ATX inhibitors with even below 1 nM in vitro activities. Two optimal entities were advanced to a bleomycin-induced mice pulmonary fibrosis model, which exerted promising efficacy in alleviating the damaged lung texture caused by bleomycin exposure. The novel carbamate-containing indole-based ATX inhibitors with a concrete binding mode may contribute to the identification of potential therapeutic agents to intervene in fibrotic diseases.

  DOI：

  10.1021/acs.jmedchem.0c00506

文献信息

• Thiazolyl urea compounds and methods of uses
  申请人：——

  公开号：US20020193405A1

  公开（公告）日：2002-12-19

  Selected novel urea compounds are effective for prophylaxis and treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stoke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  选定的新型尿素化合物对预防和治疗疾病有效，如细胞增殖或凋亡介导的疾病。该发明涵盖了新型化合物、类似物、前药和其药用可接受的盐，以及用于预防和治疗中风、癌症等疾病和其他疾病或病况的药物组合物和方法。该发明还涉及制备此类化合物的方法，以及在这些过程中有用的中间体。
• Copper-catalyzed formation of dihydrothiazoles and functionalization through subsequent ene reactions
  作者：David R. Shea、James M. Lanning、Mark J. Ferraro、Joseph M. Fose、Michael W. Fennie

  DOI：10.1016/j.tetlet.2023.154787

  日期：2023.11

  Propargyl thioimidates synthesized from readily-available starting materials are cyclized into non-aromatic dihydrothiazoles with high chemoselectivity using copper (I) iodide as a catalyst. These molecules engage in ene-type reactions with aldehyde, imine, and azo reacting partners with concomitant aromatization. A one-pot tandem hydroamination/ene process has been developed.

  使用碘化亚铜 (I) 作为催化剂，由易于获得的起始原料合成的硫代亚胺炔丙酯环化为具有高化学选择性的非芳香族二氢噻唑。这些分子与醛、亚胺和偶氮反应伙伴进行烯型反应，并伴随芳构化。已经开发出一锅串联加氢胺化/烯工艺。
• US6645990B2
  申请人：——

  公开号：US6645990B2

  公开（公告）日：2003-11-11
• US7196104B2
  申请人：——

  公开号：US7196104B2

  公开（公告）日：2007-03-27
• Discovery of Novel Indole-Based Allosteric Highly Potent ATX Inhibitors with Great <i>In Vivo</i> Efficacy in a Mouse Lung Fibrosis Model
  作者：Hongrui Lei、Ming Guo、Xiaopeng Li、Fang Jia、Changtao Li、Yu Yang、Meng Cao、Nan Jiang、Enlong Ma、Xin Zhai

  DOI：10.1021/acs.jmedchem.0c00506

  日期：2020.7.9

  Autotaxin (ATX) is the dominant catalytic enzyme accounting for the lipid mediator lysophosphatidic acid (LPA) through hydrolysis of lysophosphatidylcholine (LPC). There is great interest in developing nonacidic ATX inhibitors with a specific binding mode to serve as potential in vivo effective therapeutic tools. Herein, dating from a high-throughput screening (HTS) product Indole-1 (740 nM), a dedicated optimization campaign was implemented through derivatizing the -COOH group to versatile linkers that well-bridged the indole skeleton and the hydrophobic pocket binding groups. Ultimately, it was established that the coexistence of a carbamate linker and -OH-group-containing amines could generally furnish excellent indole-based ATX inhibitors with even below 1 nM in vitro activities. Two optimal entities were advanced to a bleomycin-induced mice pulmonary fibrosis model, which exerted promising efficacy in alleviating the damaged lung texture caused by bleomycin exposure. The novel carbamate-containing indole-based ATX inhibitors with a concrete binding mode may contribute to the identification of potential therapeutic agents to intervene in fibrotic diseases.