4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]benzaldehyde | 874901-18-5

• 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
• 英文名称: 4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]benzaldehyde
• 英文别名: 4-[2-(1,3-dioxoisoindol-2-yl)ethyl]benzaldehyde
• CAS: 874901-18-5
• 化学式: C₁₇H₁₃NO₃
• 分子量: 279.295
• InChiKey: GDHDXLLZNZUKGT-UHFFFAOYSA-N

物化性质

• 沸点：
  474.8±28.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]benzaldehyde 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 50.0 ℃ 、405.33 kPa 条件下， 反应 20.25h， 生成 N-(4-{2-[4-(2-aminoethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide
  参考文献：
  名称：

  Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema

  摘要：

  Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema.In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC50 of 230 nM; rat IC50 of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.025
• 作为产物：
  描述：

  potassium phtalimide 、 4-(2-溴乙基)苯甲醛 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以37%的产率得到4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]benzaldehyde
  参考文献：
  名称：

  Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema

  摘要：

  Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema.In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC50 of 230 nM; rat IC50 of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.025

文献信息

• Thiazole Derivatives Having Vap-1 Inhibitory Activity
  申请人：Inoue Takayuki

  公开号：US20070254931A1

  公开（公告）日：2007-11-01

  A compound of the formula (I), (II), (III) or (IV): wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof useful as a vascular adhesion protein-1 (VAP-1) inhibitor, a pharmaceutical composition, a method for preventing or treating a VAP-1 associated disease, especially macular edema, which method includes administering an effective amount of the compound or a pharmaceutically acceptable salt thereof to a subject, and the like.

  公式（I），（II），（III）或（IV）的化合物：其中每个符号如规范中所定义，或其药学上可接受的盐，可用作血管黏附蛋白-1（VAP-1）抑制剂，制药组合物，预防或治疗VAP-1相关疾病，特别是黄斑水肿的方法，该方法包括向受试者投予化合物或其药学上可接受的盐的有效量等。
• [EN] THIAZOLE DERIVATIVES HAVING VAP-1 INHIBITORY ACTIVITY<br/>[FR] DERIVES DE THIAZOLE PRESENTANT UNE ACTIVITE D'INHIBITION DE LA VAP-1
  申请人：ASTELLAS PHARMA INC

  公开号：WO2006011631A3

  公开（公告）日：2006-04-20
• [EN] THIAZOLE DERIVATIVES HAVING VAP-1 IHIBITORY ACTIVITY<br/>[FR] DERIVES DU THIAZOLE PRESENTANT UNE ACTIVITE INHIBITRICE DE LA PROTEINE 1 D'ADHESION VASCULAIRE
  申请人：ASTELLAS PHARMA INC

  公开号：WO2006028269A3

  公开（公告）日：2006-06-29
• THIAZOLE DERIVATIVES HAVING VAP-1 INHIBITORY ACTIVITY
  申请人：Astellas Pharma Inc.

  公开号：EP1786792B1

  公开（公告）日：2009-04-08
• Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema
  作者：Takayuki Inoue、Masataka Morita、Takashi Tojo、Kousei Yoshihara、Akira Nagashima、Ayako Moritomo、Mitsuru Ohkubo、Hiroshi Miyake

  DOI：10.1016/j.bmc.2012.12.025

  日期：2013.3

  Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema.In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC50 of 230 nM; rat IC50 of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats. (C) 2013 Elsevier Ltd. All rights reserved.