(Z)-[3,5-di-tert-amyl-2-(2,2-difluoroethoxy)phenyl]but-2-en-1-al | 566913-74-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂醛
• 英文名称: (Z)-[3,5-di-tert-amyl-2-(2,2-difluoroethoxy)phenyl]but-2-en-1-al
• 英文别名: (Z)-3-[2-(2,2-difluoroethoxy)-3,5-bis(2-methylbutan-2-yl)phenyl]but-2-enal
• CAS: 566913-74-4
• 化学式: C₂₂H₃₂F₂O₂
• 分子量: 366.492
• InChiKey: UUWCMXSXBNAABO-GDNBJRDFSA-N

物化性质

• 沸点：
  435.3±45.0 °C(Predicted)
• 密度：
  1.001±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-[3,5-di-tert-amyl-2-(2,2-difluoroethoxy)phenyl]but-2-en-1-al 在 N,N-二甲基丙烯基脲 、 lithium hydroxide 、 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 0.5h， 生成 (2E,4E,6Z)-7-[2-(2,2-Difluoro-ethoxy)-3,5-bis-(1,1-dimethyl-propyl)-phenyl]-3-methyl-octa-2,4,6-trienoic acid
  参考文献：
  名称：

  Novel (2E,4E,6Z)-7-(2-Alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic Acid Retinoid X Receptor Modulators Are Active in Models of Type 2 Diabetes

  摘要：

  Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.

  DOI：

  10.1021/jm020340q
• 作为产物：
  描述：

  2,4-二叔戊基苯酚 在 N-碘代丁二酰亚胺 、 正丁基锂 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 氢化铝钠 、 caesium carbonate 、 对甲苯磺酸 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 (Z)-[3,5-di-tert-amyl-2-(2,2-difluoroethoxy)phenyl]but-2-en-1-al
  参考文献：
  名称：

  Novel (2E,4E,6Z)-7-(2-Alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic Acid Retinoid X Receptor Modulators Are Active in Models of Type 2 Diabetes

  摘要：

  Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.

  DOI：

  10.1021/jm020340q

文献信息

• Novel (2<i>E</i>,4<i>E</i>,6<i>Z</i>)-7-(2-Alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic Acid Retinoid X Receptor Modulators Are Active in Models of Type 2 Diabetes
  作者：P. Y. Michellys、R. J. Ardecky、J. H. Chen、D. L. Crombie、G. J. Etgen、A. L. Faulkner、M. M. Faul、T. A. Grese、R. A. Heyman、D. S. Karanewsky、K. Klausing、M. D. Leibowitz、S. Liu、D. A. Mais、C. M. Mapes、K. B. Marschke、A. Reifel-Miller、K. M. Ogilvie、D. Rungta、A. W. Thompson、J. S. Tyhonas、M. F. Boehm

  DOI：10.1021/jm020340q

  日期：2003.6.1

  Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.