2-甲基-3氧-2,3-二氢-1氢-异吲哚-4-羧酸 | 14262-20-5

• 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: 2-甲基-3氧-2,3-二氢-1氢-异吲哚-4-羧酸
• 英文名称: 2-Methyl-3-oxo-4-isoindolin-carbonsaeure
• 英文别名: 2-methyl-3-oxo-1,3-dihydro-isoindole-4-carboxylic acid；2-Methyl-3-oxoisoindoline-4-carboxylic acid；2-methyl-3-oxo-1H-isoindole-4-carboxylic acid
• CAS: 14262-20-5
• 化学式: C₁₀H₉NO₃
• mdl: MFCD03821905
• 分子量: 191.186
• InChiKey: DUMZHWJYINJEAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl-(4-amino-4-(4-methoxy-1-methylbenzo[d]imidazol-2-yl)butyl)carbamate-L-ornithine 、 2-甲基-3氧-2,3-二氢-1氢-异吲哚-4-羧酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Development of a Selective Inhibitor of Protein Arginine Deiminase 2

  摘要：

  Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy. Herein, we demonstrate that substitutions at both the N-terminus and C-terminus of Cl-amidine result in >100-fold increases in PAD2 potency and selectivity (30a, 41a, and 49a) as well as cellular efficacy (30a). Notably, these compounds use the far less reactive fluoroacetamidine warhead. In total, we predict that 30a will be a critical tool for understanding cellular PAD2 function and sets the stage for treating diseases in which PAD2 activity is dysregulated.

  DOI：

  10.1021/acs.jmedchem.7b00274

文献信息

• Heterocyclic Compound
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20180155333A1

  公开（公告）日：2018-06-07

  The present invention provide a compound having an orexin receptor antagonistic activity, which is expected to be useful as medicaments such as agents for the prophylaxis or treatment of sleep disorder, depression, anxiety disorder, panic disorder, schizophrenia, drug dependence, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种具有促醒素受体拮抗活性的化合物，预计可用作药物，如预防或治疗睡眠障碍、抑郁症、焦虑症、恐慌症、精神分裂症、药物依赖、阿尔茨海默病等的药剂。 本发明涉及由以下式（I）表示的化合物： 其中每个符号如规范中定义，或其盐。
• POLY(ADP-RIBOSE)POLYMERASE INHIBITORS
  申请人：Gandhi B. Virajkumar

  公开号：US20080108659A1

  公开（公告）日：2008-05-08

  Compounds which inhibit the activity of poly(ADP-ribose)polymerase, compositions containing the compounds and methods of treating diseases using the compounds is disclosed.

  抑制聚(ADP-核糖)聚合酶活性的化合物、含有这些化合物的组合物以及使用这些化合物治疗疾病的方法被披露。
• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3287454B1

  公开（公告）日：2020-09-02
• US8143284B2
  申请人：——

  公开号：US8143284B2

  公开（公告）日：2012-03-27
• Development of a Selective Inhibitor of Protein Arginine Deiminase 2
  作者：Aaron Muth、Venkataraman Subramanian、Edward Beaumont、Mitesh Nagar、Philip Kerry、Paul McEwan、Hema Srinath、Kathleen Clancy、Sangram Parelkar、Paul R. Thompson

  DOI：10.1021/acs.jmedchem.7b00274

  日期：2017.4.13

  Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy. Herein, we demonstrate that substitutions at both the N-terminus and C-terminus of Cl-amidine result in >100-fold increases in PAD2 potency and selectivity (30a, 41a, and 49a) as well as cellular efficacy (30a). Notably, these compounds use the far less reactive fluoroacetamidine warhead. In total, we predict that 30a will be a critical tool for understanding cellular PAD2 function and sets the stage for treating diseases in which PAD2 activity is dysregulated.