1,3-Bis({7-[(3-hydroxyphenyl)sulfamoyl]naphthalen-2-yl})urea | 309932-51-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1,3-Bis({7-[(3-hydroxyphenyl)sulfamoyl]naphthalen-2-yl})urea
• 英文别名: 1,3-bis[7-[(3-hydroxyphenyl)sulfamoyl]naphthalen-2-yl]urea
• CAS: 309932-51-2
• 化学式: C₃₃H₂₆N₄O₇S₂
• 分子量: 654.724
• InChiKey: IXGUFRNFJCNGSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  46
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  191
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-[7-(chlorosulfonyl)(2-naphthyl)]{[7-(chlorosulfonyl)(2-naphthyl)]amino}carboxamide 、 3-氨基苯酚 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 1,3-Bis({7-[(3-hydroxyphenyl)sulfamoyl]naphthalen-2-yl})urea
  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

• NAPHTHALENE UREAS AS GLUCOSE UPTAKE ENHANCERS
  申请人：TELIK, INC.

  公开号：EP1181271B1

  公开（公告）日：2005-01-19
• US6458998B1
  申请人：——

  公开号：US6458998B1

  公开（公告）日：2002-10-01
• US7071231B2
  申请人：——

  公开号：US7071231B2

  公开（公告）日：2006-07-04
• 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.