1-methyl-1,3-dihydrobenzo[c]isothiazole-5-carboxylic acid 2,2-dioxide | 41713-65-9

• 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: 1-methyl-1,3-dihydrobenzo[c]isothiazole-5-carboxylic acid 2,2-dioxide
• 英文别名: 1-methyl-1,3-dihydro-2,1-benzothiazole-5-carboxylic acid 2,2-dioxide；1-methyl-2,2-dioxo-2,3-dihydro-1H-2λ⁶-benzo[c]isothiazole-5-carboxylic acid；1-methyl-2,2-dioxo-3H-2,1-benzothiazole-5-carboxylic acid
• CAS: 41713-65-9
• 化学式: C₉H₉NO₄S
• 分子量: 227.241
• InChiKey: ASINZLYDRJSZMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-amino-4-methylphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide 、 1-methyl-1,3-dihydrobenzo[c]isothiazole-5-carboxylic acid 2,2-dioxide 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以57%的产率得到N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-1-methyl-1,3-dihydrobenzo[c]isothiazole-5-carboxamide-2,2-dioxide
  参考文献：
  名称：

  [EN] FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1
  [FR] DÉRIVÉS DE 1,4-DIHYDRODIOXINE FUSIONNÉS À UTILISER EN TANT QU'INHIBITEURS DE FACTEUR DE TRANSCRIPTION 1 DU CHOC THERMIQUE

  摘要：

  本发明涉及式I的化合物，其中A1、A2、R4和Q如本文所定义。本发明的化合物是热休克因子1（HSF1）的抑制剂。具体来说，本发明涉及将这些化合物用作治疗和/或预防增殖性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的方法，以及包含它们的药物组合物。

  公开号：

  WO2015049535A1
• 作为产物：
  描述：

  1-Methyl-5-acetyl-2,1-benzisohiazolin-2,2-dioxid 在 氢氧化钾 、 溴 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-methyl-1,3-dihydrobenzo[c]isothiazole-5-carboxylic acid 2,2-dioxide
  参考文献：
  名称：

  Skorcz,J.A. et al., Journal of Heterocyclic Chemistry, 1973, vol. 10, p. 249 - 253

  摘要：

  DOI：

文献信息

• Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold
  作者：Junya Kawai、Masahiro Ota、Hitoshi Ohki、Tadashi Toki、Makoto Suzuki、Takashi Shimada、Satoshi Matsui、Hidekazu Inoue、Chika Sugihara、Norikazu Matsuhashi、Yumi Matsui、Sachiko Takaishi、Kiyoshi Nakayama

  DOI：10.1021/acsmedchemlett.9b00069

  日期：2019.6.13

  Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays a key role in one-carbon (1C) metabolism in human mitochondria, and its high expression correlates with poor survival of patients with various types of cancer. An isozyme-selective MTHFD2 inhibitor is highly attractive for potential use in cancer treatment. Herein, we disclose a novel isozyme-selective MTHFD2 inhibitor DS44960156, with a tricyclic coumarin

  亚甲基四氢叶酸脱氢酶2（MTHFD2）在人类线粒体中的一碳（1C）代谢中起关键作用，其高表达与各种类型癌症患者的不良生存率相关。同工酶选择性MTHFD2抑制剂对于潜在地用于癌症治疗具有很高的吸引力。本文中，我们公开了具有三环香豆素骨架的新型同工酶选择性MTHFD2抑制剂DS44960156，该骨架最初是通过高通量筛选（HTS）发现的，并使用基于结构的药物设计（SBDD）进行了改进。DS44960156将基于以下特征为进一步优化提供一个良好的起点：（1）MTHFD2相对于MTHFD1具有前所未有的选择性（> 18倍）；（2）分子量小于400；以及（3）良好的配体效率（LE）。
• Fused 1,4-dihydrodioxin derivatives as inhibitors of heat shock transcription factor I
  申请人：Cancer Research Technology Limited

  公开号：US10189821B2

  公开（公告）日：2019-01-29

  The present invention relates to compounds of formula I as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及本文定义的式 I 化合物。本发明的化合物是热休克因子 1（HSF1）的抑制剂。特别是，本发明涉及将这些化合物用作治疗剂来治疗和/或预防增殖性疾病，如癌症。本发明还涉及这些化合物的制备工艺以及包含这些化合物的药物组合物。
• FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1
  申请人：Cancer Research Technology Limited

  公开号：EP3052492A1

  公开（公告）日：2016-08-10
• FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR I
  申请人：Cancer Research Technology Limited

  公开号：US20170037036A1

  公开（公告）日：2017-02-09

  The present invention relates to compounds of formula I as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.
• INHIBITOR COMPOUNDS
  申请人：Cancer Research Technology Limited

  公开号：US20190106413A1

  公开（公告）日：2019-04-11

  The present invention relates to compounds of formula I as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.