(Z)-3-[3,5-di-tert-butyl-2-(2,2-difluoroethoxy)phenyl]but-2-en-1-al | 330935-85-8

• 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-difluoroethoxy)phenyl]but-2-en-1-al
• 英文别名: (Z)-3-[3,5-ditert-butyl-2-(2,2-difluoroethoxy)phenyl]but-2-enal
• CAS: 330935-85-8
• 化学式: C₂₀H₂₈F₂O₂
• 分子量: 338.438
• InChiKey: FCNZHTUTJVMMCS-JYRVWZFOSA-N

物化性质

• 沸点：
  407.7±45.0 °C(Predicted)
• 密度：
  1.017±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  24
• 可旋转键数：
  7
• 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：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-3-[3,5-di-tert-butyl-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 LG101506
  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-[3,5-di-tert-butyl-2-(2,2-difluoroethoxy)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95%的产率得到(Z)-3-[3,5-di-tert-butyl-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

• Fluorinated trienes and their use as rxr modulators
  申请人：——

  公开号：US20040248919A1

  公开（公告）日：2004-12-09

  The present invention relates to a method of modulating retinoid X receptor activity in a mammal, novel compounds and pharmaceutical compositions for modulating retinoid X receptor activity in a mammal, and methods of making compounds that modulate retinoid X receptor activity in a mammal. The compounds are represented by Structural Formula 1: The compounds of Structural Formual 1 are efficacious insulin sensitizers and do not have the undesirable side effects of increasing triglycerides or suppressing the thyroid hormone axis. 1

  本发明涉及一种调节哺乳动物中视黄醇X受体活性的方法，用于调节哺乳动物中视黄醇X受体活性的新型化合物和制备调节哺乳动物中视黄醇X受体活性的化合物的方法。这些化合物由结构式1表示：结构式1的化合物是有效的胰岛素敏化剂，并且不具有增加三酰甘油或抑制甲状腺激素轴的不良副作用。
• Design and synthesis of fluorinated RXR modulators
  作者：D.L. Gernert、R. Ajamie、R.A. Ardecky、M.G. Bell、M.D. Leibowitz、D.A. Mais、C.M. Mapes、P.Y. Michellys、D. Rungta、A. Reifel-Miller、J.S. Tyhonas、N. Yumibe、T.A. Grese

  DOI：10.1016/s0960-894x(03)00703-0

  日期：2003.10

  Fluorinated trienoic acid analogues of the RXR selective modulator 1 (LG101506) were synthesized, and tested for their ability to bind RXRalpha and activate RXR homo and heterodimers. Potency and efficacy were observed to be dependent upon the position of fluorination, and improvement in pharmacological profile was demonstrated in some cases. (C) 2003 Elsevier Ltd. All rights reserved.
• FLUORINATED TRIENES AND THEIR USE AS RXR MODULATORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1368296A1

  公开（公告）日：2003-12-10
• [EN] FLUORINATED TRIENES AND THEIR USE AS RXR MODULATORS<br/>[FR] TRIENES FLUORES ET LEUR UTILISATION EN TANT QUE MODULATEURS DE RXR
  申请人：LILLY CO ELI

  公开号：WO2002072528A1

  公开（公告）日：2002-09-19

  The present invention relates to a method of modulating retinoid X receptor activity in a mammal, novel compounds and pharmaceutical compositions for modulating retinoid X receptor activity in a mammal, and methods of making compounds that modulate retinoid X receptor activity in a mammal. The compounds are represented by Structural Formula 1: The compounds of Structural Formual 1 are efficacious insulin sensitizers and do not have the undesirable side effects of increasing triglycerides or suppressing the thyroid hormone axis.
• 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.