3-氧代-2,3-二氢-1H-异吲哚-5-羧酸甲酯 | 954239-52-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 3-氧代-2,3-二氢-1H-异吲哚-5-羧酸甲酯
• 中文别名: 3-氧代异吲哚啉-5-甲酸甲酯
• 英文名称: methyl 3-oxoisoindoline-5-carboxylate
• 英文别名: methyl 3-oxo-1,2-dihydroisoindole-5-carboxylate
• CAS: 954239-52-2
• 化学式: C₁₀H₉NO₃
• mdl: MFCD09878911
• 分子量: 191.186
• InChiKey: FOUXXPLZXKYJRB-UHFFFAOYSA-N

物化性质

• 沸点：
  462.2±45.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933790090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-氧代-2,3-二氢-1H-异吲哚-5-羧酸甲酯 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 32.0h， 生成 2-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-oxoisoindoline-5-carboxylic acid
  参考文献：
  名称：

  ASK1 INHIBITOR COMPOUNDS AND USES THEREOF

  摘要：

  本发明涉及化合物，包括药物可接受的盐、溶剂化物、代谢物、前药等，以及制造这些化合物的方法，包含这些化合物的药物组合物，以及使用这些化合物治疗非酒精性脂肪肝炎和其他以组织修复功能异常和纤维化为特征的疾病的方法。

  公开号：

  US20180291002A1
• 作为产物：
  描述：

  methyl 2-tert-butyl-3-oxo-1H-isoindole-5-carboxylate 在 三氟乙酸 作用下， 反应 96.0h， 以95%的产率得到3-氧代-2,3-二氢-1H-异吲哚-5-羧酸甲酯
  参考文献：
  名称：

  Carbamoyl radicals from carbamoylxanthates: a facile entry into isoindolin-1-ones

  摘要：

  It has been found that carbamoylxanthates derived from secondary t-butyl amines are stable compounds which function as efiicient sources of carbamoyl radicals. The carbamoylxanthates derived from t-butylbenzylamines can be efficiently transformed into 2- t-butylisoindolin-1-ones via an oxidative radical cyclization process. The carbamoylxanthates derived from N-t-butylamino olefins underwent the expected cyclization/xanthate-transfer process to afford the corresponding pyrrolidones and piperidones under thermally induced DLP fragmentation conditions and in the presence of catalytic Et3B in air, at room temperature. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.09.142

文献信息

• [EN] APOPTOSIS SIGNAL-REGULATING KINASE 1 INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE KINASE 1 DE RÉGULATION DU SIGNAL APOPTOTIQUE, ET LEURS MÉTHODES D'UTILISATION
  申请人：ENANTA PHARM INC

  公开号：WO2018218051A1

  公开（公告）日：2018-11-29

  The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof: which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

  本发明公开了化合物的结构式（I），以及其药学上可接受的盐和酯：这些化合物抑制凋亡信号调节激酶1（ASK-1），与自身免疫性疾病、神经退行性疾病、炎症性疾病、慢性肾脏疾病、心血管疾病相关。本发明还涉及包括上述化合物的药物组合物，用于治疗患有ASK-1相关疾病的受试者。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的ASK-1相关疾病的方法。本发明具体涉及治疗与肝脂肪变性相关的ASK-1的方法，包括非酒精性脂肪肝病（NAFLD）和非酒精性脂肪性肝炎病（NASH）。
• [EN] CONJUGATES COMPRISING RIPK2 INHIBITORS<br/>[FR] CONJUGUÉS COMPRENANT DES INHIBITEURS DE RIPK2
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017182418A1

  公开（公告）日：2017-10-26

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

  本发明涉及化合物、组合物、组合物和含有所述化合物的药物以及其制备方法。该发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为RIP2激酶活性的抑制剂，包括降解RIP2激酶，用于治疗由RIP2激酶介导的疾病和症状，特别是用于治疗炎症性疾病或症状。
• Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
  申请人：ENANTA PHARMACEUTICALS, INC.

  公开号：US10450301B2

  公开（公告）日：2019-10-22

  The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof: which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

  本发明公开了式 (I) 化合物及其药学上可接受的盐和酯： 其抑制与自身免疫性疾病、神经退行性疾病、炎症性疾病、慢性肾病、心血管疾病相关的凋亡信号调节激酶1（ASK-1）。本发明进一步涉及包含上述化合物的药物组合物，用于给患有 ASK-1 相关疾病的患者用药。本发明还涉及通过施用包含本发明化合物的药物组合物治疗受试者 ASK-1 相关疾病的方法。本发明特别涉及治疗与肝脂肪变性相关的ASK-1的方法，包括非酒精性脂肪肝（NAFLD）和非酒精性脂肪性肝炎（NASH）。
• Conjugates comprising RIPK2 inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10781205B2

  公开（公告）日：2020-09-22

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

  本发明涉及含有所述化合物的化合物、组合物、组合物和药物及其制备工艺。 本发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为 RIP2 激酶活性的抑制剂，包括降解 RIP2 激酶，治疗由 RIP2 激酶介导的疾病和病症，特别是治疗炎症性疾病或病症。
• Carbamoyl radicals from carbamoylxanthates: a facile entry into isoindolin-1-ones
  作者：Germán López-Valdez、Simón Olguín-Uribe、Luis D. Miranda

  DOI：10.1016/j.tetlet.2007.09.142

  日期：2007.11

  It has been found that carbamoylxanthates derived from secondary t-butyl amines are stable compounds which function as efiicient sources of carbamoyl radicals. The carbamoylxanthates derived from t-butylbenzylamines can be efficiently transformed into 2- t-butylisoindolin-1-ones via an oxidative radical cyclization process. The carbamoylxanthates derived from N-t-butylamino olefins underwent the expected cyclization/xanthate-transfer process to afford the corresponding pyrrolidones and piperidones under thermally induced DLP fragmentation conditions and in the presence of catalytic Et3B in air, at room temperature. (C) 2007 Elsevier Ltd. All rights reserved.