(Z)-3-[3,5-di-tert-butyl-2-(2,2,2-trifluoroethoxy)phenyl]but-2-en-1-al | 566913-84-6

• 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-[3,5-di-tert-butyl-2-(2,2,2-trifluoroethoxy)phenyl]but-2-en-1-al
• 英文别名: (Z)-3-[3,5-ditert-butyl-2-(2,2,2-trifluoroethoxy)phenyl]but-2-enal
• CAS: 566913-84-6
• 化学式: C₂₀H₂₇F₃O₂
• 分子量: 356.428
• InChiKey: REMZPMDUVJPLTI-JYRVWZFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-3-[3,5-di-tert-butyl-2-(2,2,2-trifluoroethoxy)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-[3,5-Di-tert-butyl-2-(2,2,2-trifluoro-ethoxy)-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：

  (Z)-[3,5-di-tert-butyl-2-(2,2,2-trifluoroethoxy)phenyl]but-2-en-1-ol 在 N-甲基吲哚酮 、 四丙基高钌酸铵 作用下， 以 二氯甲烷 为溶剂， 以94%的产率得到(Z)-3-[3,5-di-tert-butyl-2-(2,2,2-trifluoroethoxy)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