4-(3,5-dichloro-phenyl)-[1,2]naphthoquinone

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(3,5-dichloro-phenyl)-[1,2]naphthoquinone
• 英文别名: 4-(3,5-dichlorophenyl)naphthalene-1,2-dione
• 化学式: C₁₆H₈Cl₂O₂
• 分子量: 303.144
• InChiKey: UFYANOOIIMVQHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-Brom-1,2-naphthochinon 、 3,5-二氯苯硼酸 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 4-(3,5-dichloro-phenyl)-[1,2]naphthoquinone
  参考文献：
  名称：

  Potent Reversible Inhibitors of the Protein Tyrosine Phosphatase CD45

  摘要：

  The cytosolic portion of CD45, a major transmembrane glycoprotein found on nucleated hematopoietic cells, contains protein tyrosine phosphatase activity and is critical for T-cell receptor-mediated T-cell activation. CD45 inhibitors could have utility in the treatment of autoimmune disorders and organ graft rejection. A number of 9, l0-phenanthrenediones were identified that reversibly inhibited CD45-mediated p-nitrophenyl phosphate (pNPP) hydrolysis. Chemistry efforts around the 9,10-phenanthrenedione core led to the most potent inhibitors known to date. In a functional assay, the compounds were also potent inhibitors of T-cell receptor-mediated proliferation, with activities in the low micromolar range paralleling their enzyme inhibition. It was also discovered that the nature of modification to the phenanthrenedione pharmacophore could affect selectivity for CD45 over PTP1B (protein tyrosine phosphatase 1B) or vice versa.

  DOI：

  10.1021/jm000447i

文献信息

• Cd45 inhibitors
  申请人：——

  公开号：US20030119897A1

  公开（公告）日：2003-06-26

  Substituted naphthalenediones in accord with structural diagram (I): compositions thereof and methods for the use thereof, for the treatment of T cell mediated conditions such as autoimmune diseases and organ graft rejection. In compounds of the invention, wherein: Q 1 at each occurrence is independently selected from hydrogen, hydroxy, halogen, C(O)O(C 1 -C 3 ) alkyl and C(O)phenyl, and Q 2 is selected from hydrogen, halogen, O—(C 1 -C 3 )alkyl, O—(C 1 -C 3 )alkenyl, phenyl, indolyl and naphthyl, where phenyl may be mono- or di-substituted with NO 2 or halogen, and indolyl may be substituted with (C 1 -C 3 )alkyl or phenyl.

  根据结构图(I)中的取代萘酮：其组成物及其使用方法，用于治疗T细胞介导的疾病，如自身免疫疾病和器官移植排斥。在本发明的化合物中，其中：Q1在每次出现时独立地选择自氢、羟基、卤素、C(O)O(C1-C3)烷基和C(O)苯基，Q2选择自氢、卤素、O-(C1-C3)烷基、O-(C1-C3)烯基、苯基、吲哚基和萘基，其中苯基可能单取代或双取代为NO2或卤素，吲哚基可能被(C1-C3)烷基或苯基取代。
• NAPHTHOQUINONE DERIVATIVES AS CD45 INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP1259231A2

  公开（公告）日：2002-11-27
• US6939896B2
  申请人：——

  公开号：US6939896B2

  公开（公告）日：2005-09-06
• [EN] CD45 INHIBITORS<br/>[FR] INHIBITEURS CD45
  申请人：ASTRAZENECA AB

  公开号：WO2001045681A2

  公开（公告）日：2001-06-28

  Substituted naphthalenediones in accord with structural diagram (I): compositions thereof and methods for the use thereof, for the treatment of T cell mediated conditions such as autoimmune diseases and organ graft rejection. In compounds of the invention, wherein: Q1 at each occurrence is independently selected from hydrogen, hydroxy, halogen, C(O)O(C¿1?-C3) alkyl and C(O)phenyl, and Q?2¿ is selected from hydrogen, halogen, O-(C¿1?-C3)alkyl, O-(C1-C3)alkenyl, phenyl, indolyl and naphthyl, where phenyl may be mono- or di-substituted with NO2 or halogen, and indolyl may be substituted with (C1-C3)alkyl or phenyl.
• Potent Reversible Inhibitors of the Protein Tyrosine Phosphatase CD45
  作者：Rebecca A. Urbanek、Suzanne J. Suchard、Gary B. Steelman、Katharine S. Knappenberger、Linda A. Sygowski、Chris A. Veale、Marc J. Chapdelaine

  DOI：10.1021/jm000447i

  日期：2001.5.1

  The cytosolic portion of CD45, a major transmembrane glycoprotein found on nucleated hematopoietic cells, contains protein tyrosine phosphatase activity and is critical for T-cell receptor-mediated T-cell activation. CD45 inhibitors could have utility in the treatment of autoimmune disorders and organ graft rejection. A number of 9, l0-phenanthrenediones were identified that reversibly inhibited CD45-mediated p-nitrophenyl phosphate (pNPP) hydrolysis. Chemistry efforts around the 9,10-phenanthrenedione core led to the most potent inhibitors known to date. In a functional assay, the compounds were also potent inhibitors of T-cell receptor-mediated proliferation, with activities in the low micromolar range paralleling their enzyme inhibition. It was also discovered that the nature of modification to the phenanthrenedione pharmacophore could affect selectivity for CD45 over PTP1B (protein tyrosine phosphatase 1B) or vice versa.