6-氯-3-甲基苯并[b]噻吩-2-羧酸甲酯 | 1415968-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 6-氯-3-甲基苯并[b]噻吩-2-羧酸甲酯
• 英文名称: methyl 6-chloro-3-methylbenzo[b]thiophene-2-carboxylate
• 英文别名: Methyl 6-chloro-3-methylbenzo[B]thiophene-2-carboxylate；methyl 6-chloro-3-methyl-1-benzothiophene-2-carboxylate
• CAS: 1415968-74-9
• 化学式: C₁₁H₉ClO₂S
• 分子量: 240.71
• InChiKey: GIWWBGTXBMMEJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  6-氯-3-甲基苯并[b]噻吩-2-羧酸甲酯 在 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 4.5h， 生成 6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)benzo[b]thiophene-2-carboxylic acid
  参考文献：
  名称：

  Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design

  摘要：

  Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family of proteins, is overexpressed and amplified in various cancers and promotes the aberrant survival of tumor cells that otherwise would undergo apoptosis. Here we describe the discovery of potent and selective Mcl-1 inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified two chemically distinct hit series that bind to different sites on Mcl-1. Members of the two fragment classes were merged together to produce lead compounds that bind to Mcl-1 with a dissociation constant of <100 nM with selectivity for Mcl-1 over Bcl-xL and Bcl-2. Structures of merged compounds when complexed to Mcl-1 were obtained by X-ray crystallography and provide detailed information about the molecular recognition of small-molecule ligands binding Mcl-1. The compounds represent starting points for the discovery of clinically useful Mcl-1 inhibitors for the treatment of a wide variety of cancers.

  DOI：

  10.1021/jm301448p
• 作为产物：
  描述：

  4'-氯-2'-氟苯乙酮 、 巯基乙酸甲酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 6-氯-3-甲基苯并[b]噻吩-2-羧酸甲酯
  参考文献：
  名称：

  [EN] AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS
  [FR] COMPOSÉS D'AMINOISOXAZOLINE EN TANT QUE RÉCEPTEURS NICOTINIQUES ALPHA7 DE L'ACÉTYLCHOLINE

  摘要：

  本发明涉及新型氨基异噁唑啉化合物及其药物组合物，适用作α7-nAChR的激动剂或部分激动剂，以及制备这些化合物和组合物的方法，以及在维持、治疗和/或改善认知功能的方法中使用这些化合物和组合物，特别是将该化合物或组合物用于需要的患者的给药方法，例如患有认知缺陷和/或希望增强认知功能的患者，可能从中获益。

  公开号：

  WO2017069980A1

文献信息

• [EN] AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS<br/>[FR] COMPOSÉS D'AMINOISOXAZOLINE EN TANT QUE RÉCEPTEURS NICOTINIQUES ALPHA7 DE L'ACÉTYLCHOLINE
  申请人：FORUM PHARMACEUTICALS INC

  公开号：WO2017069980A1

  公开（公告）日：2017-04-27

  The present invention relates to novel aminoisoxazoline compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.

  本发明涉及新型氨基异噁唑啉化合物及其药物组合物，适用作α7-nAChR的激动剂或部分激动剂，以及制备这些化合物和组合物的方法，以及在维持、治疗和/或改善认知功能的方法中使用这些化合物和组合物，特别是将该化合物或组合物用于需要的患者的给药方法，例如患有认知缺陷和/或希望增强认知功能的患者，可能从中获益。
• SUBSTITUTED BENZOFURAN, BENZOTHIOPHENE AND INDOLE MCL-1 INHIBITORS
  申请人：VANDERBILT UNIVERSITY

  公开号：US20150336925A1

  公开（公告）日：2015-11-26

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了一种抑制抗凋亡Bcl-2家族成员髓系细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了制药组合物以及使用化合物治疗因Mcl-1蛋白过度表达或失调而表现出的疾病和症状（例如癌症）的方法。
• Substituted benzofuran, benzothiophene and indole MCL-1 inhibitors
  申请人：VANDERBILT UNIVERSITY

  公开号：US10093640B2

  公开（公告）日：2018-10-09

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了抑制抗凋亡 Bcl-2 家族成员骨髓细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了药物组合物以及使用化合物治疗以 Mcl-1 蛋白过度表达或失调为特征的疾病和病症（如癌症）的方法。
• Substituted benzofuran, benzothiophene and indole Mcl-1 inhibitors
  申请人：Vanderbilt University

  公开号：US10844032B2

  公开（公告）日：2020-11-24

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了抑制抗凋亡 Bcl-2 家族成员骨髓细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了药物组合物以及使用化合物治疗以 Mcl-1 蛋白过度表达或失调为特征的疾病和病症（如癌症）的方法。
• AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS
  申请人：Axovant Sciences GmbH

  公开号：EP3365061A1

  公开（公告）日：2018-08-29