methyl 5-({[7-(acetylamino)(2-naphthyl)]sulfonyl}amino)-2-chlorobenzoate | 1069138-81-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 5-({[7-(acetylamino)(2-naphthyl)]sulfonyl}amino)-2-chlorobenzoate
• 英文别名: Methyl 5-[(7-acetamidonaphthalen-2-yl)sulfonylamino]-2-chlorobenzoate
• CAS: 1069138-81-3
• 化学式: C₂₀H₁₇ClN₂O₅S
• 分子量: 432.884
• InChiKey: AVWYUHZCQMIDEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-({[7-(acetylamino)(2-naphthyl)]sulfonyl}amino)-2-chlorobenzoate 在 sodium hydroxide 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以95%的产率得到5-{[(7-amino(2-naphthyl))sulfonyl]amino}-2-chlorobenzoic acid
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Novel Insulin Receptor Tyrosine Kinase Activators

  摘要：

  A novel series of symmetrical ureas of [(7-amino(2-naphthyl))sulfonyl]phenylamines were designed, synthesized, and tested for their ability to increase glucose transport in mouse 3T3-L1 adipocytes, a surrogate readout for activation of the insulin receptor (IR) tyrosine kinase (IRTK). A structure-activity relationship was established that indicated glucose transport activity was dependent on the presence of two acidic functionalities, two sulfonamide linkages, and a central urea or 2-imidazolidinone core. Compound 30 was identified as a potent and selective IRTK activator. At low concentrations, 30 was able to increase the tyrosine phosphorylation of the IR stimulated by submaximal insulin. At higher concentrations, 30 was able to increase tyrosine the phosphorylation levels of the IR in the absence of insulin. When administered intraperitoneally (ip) and orally (po), 30 improved glucose tolerance in hypoinsulinemic, streptozotocin-treated rats. These data provide pharmacological validation that small molecule IRTK activators represent a potential new class of antidiabetic agents.

  DOI：

  10.1021/jm800600v
• 作为产物：
  描述：

  甲基5-氨基-2-氯苯甲酸酯 、 7-acetylamino-2-naphthalenesulfonyl chloride 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以82%的产率得到methyl 5-({[7-(acetylamino)(2-naphthyl)]sulfonyl}amino)-2-chlorobenzoate
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Novel Insulin Receptor Tyrosine Kinase Activators

  摘要：

  A novel series of symmetrical ureas of [(7-amino(2-naphthyl))sulfonyl]phenylamines were designed, synthesized, and tested for their ability to increase glucose transport in mouse 3T3-L1 adipocytes, a surrogate readout for activation of the insulin receptor (IR) tyrosine kinase (IRTK). A structure-activity relationship was established that indicated glucose transport activity was dependent on the presence of two acidic functionalities, two sulfonamide linkages, and a central urea or 2-imidazolidinone core. Compound 30 was identified as a potent and selective IRTK activator. At low concentrations, 30 was able to increase the tyrosine phosphorylation of the IR stimulated by submaximal insulin. At higher concentrations, 30 was able to increase tyrosine the phosphorylation levels of the IR in the absence of insulin. When administered intraperitoneally (ip) and orally (po), 30 improved glucose tolerance in hypoinsulinemic, streptozotocin-treated rats. These data provide pharmacological validation that small molecule IRTK activators represent a potential new class of antidiabetic agents.

  DOI：

  10.1021/jm800600v

文献信息

• Design, Synthesis, and Structure−Activity Relationships of Novel Insulin Receptor Tyrosine Kinase Activators
  作者：Robert T. Lum、Mingshan Cheng、Cristina P. Cristobal、Ira D. Goldfine、Joseph L. Evans、James G. Keck、Robert W. Macsata、Vara Prasad Manchem、Yukiharu Matsumoto、Sophia J. Park、Sandhya S. Rao、Louise Robinson、Songyuan Shi、Wayne R. Spevak、Steven R. Schow

  DOI：10.1021/jm800600v

  日期：2008.10.9

  A novel series of symmetrical ureas of [(7-amino(2-naphthyl))sulfonyl]phenylamines were designed, synthesized, and tested for their ability to increase glucose transport in mouse 3T3-L1 adipocytes, a surrogate readout for activation of the insulin receptor (IR) tyrosine kinase (IRTK). A structure-activity relationship was established that indicated glucose transport activity was dependent on the presence of two acidic functionalities, two sulfonamide linkages, and a central urea or 2-imidazolidinone core. Compound 30 was identified as a potent and selective IRTK activator. At low concentrations, 30 was able to increase the tyrosine phosphorylation of the IR stimulated by submaximal insulin. At higher concentrations, 30 was able to increase tyrosine the phosphorylation levels of the IR in the absence of insulin. When administered intraperitoneally (ip) and orally (po), 30 improved glucose tolerance in hypoinsulinemic, streptozotocin-treated rats. These data provide pharmacological validation that small molecule IRTK activators represent a potential new class of antidiabetic agents.