(E)-(S)-2-ethoxy-3-[4-(5-phenyl-pent-2-en-4-ynyloxy)-phenyl]-propionic acid ethyl ester | 351863-99-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (E)-(S)-2-ethoxy-3-[4-(5-phenyl-pent-2-en-4-ynyloxy)-phenyl]-propionic acid ethyl ester
• 英文别名: ethyl (2S)-2-ethoxy-3-[4-[(E)-5-phenylpent-2-en-4-ynoxy]phenyl]propanoate
• CAS: 351863-99-5
• 化学式: C₂₄H₂₆O₄
• 分子量: 378.468
• InChiKey: DZSYJXNOEAYDFC-LNLBBOMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-(S)-2-ethoxy-3-[4-(5-phenyl-pent-2-en-4-ynyloxy)-phenyl]-propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以225 mg (54%)的产率得到NNC 61-4655
  参考文献：
  名称：

  New compounds, their preparation and use

  摘要：

  本发明涉及式(I)的化合物。 这些化合物在治疗和/或预防由核受体介导的疾病中具有用途，特别是过氧化物酶体增殖激活受体（PPAR）。

  公开号：

  US20010041709A1
• 作为产物：
  描述：

  苯丙炔醛缩二乙醛 在 三丁基膦 、 硫酸 、 sodium ethanolate 、 二异丁基氢化铝 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 10.0h， 生成 (E)-(S)-2-ethoxy-3-[4-(5-phenyl-pent-2-en-4-ynyloxy)-phenyl]-propionic acid ethyl ester
  参考文献：
  名称：

  Process Development and Scale-Up of the PPAR Agonist NNC 61-4655

  摘要：

  A scalable synthetic route of the nonselective but PPARalpha-preferring potent PPAR agonist NNC 61-4655 aimed for treatment of type 2 diabetes was developed. The synthetic pathway comprises the convergent synthesis and coupling of the two key intermediates E-5-(chloropent-3-en-1-ynyl)benzene 8 (prepared in a five-step synthesis in 18% overall yield) and (S)-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid isopropyl ester 9. The 2-aminoethanol salt of NNC 61-4655 was selected in a preclinical salt selection program as the appropriate salt form for further development. More than 900 g of NNC 61-4655, 2-aminoethanol was finally synthesized under GMP in 98.7% purity. In comparison to the original medicinal chemistry route, starting from phenylpropargyl aldehyde 1, the overall yield towards NNC 61-4655 could be enhanced from 24 to 37%. An improved scalable two-step synthesis for 8 was developed on a laboratory scale ( greater than or equal to 33-35% overall yield) shortly after the GMP batch.

  DOI：

  10.1021/op034048j

文献信息

• Combination therapy using a dual PPAR-a/PPAR-y activator and a GLP-1 derivative for the treatment of metabolic syndrome and related diseases and disorders
  申请人：——

  公开号：US20030199451A1

  公开（公告）日：2003-10-23

  The present invention relates to a pharmaceutical composition comprising a dual Peroxisome Proliferator-Activated Receptor-alpha/Peroxisome Proliferator-Activated Receptor-gama activator (PPAR-&agr;/PPAR-&ggr;) and a Glucagon Like Peptide-1 (GLP-1) derivative for treating, preventing and reducing the risk of developing Type 2 diabetes, insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders.

  本发明涉及一种药物组成物，包括一个双过氧化物酶体增殖物激活受体-α/过氧化物酶体增殖物激活受体-γ激活剂（PPAR-α/PPAR-γ）和一种胰高血糖素样肽-1（GLP-1）衍生物，用于治疗、预防和降低发展2型糖尿病、胰岛素抵抗、血脂异常、肥胖症、高血压和其他相关疾病和障碍的风险。
• Combination therapy using a dual PPAR-α/PPAR-γ activator and a GLP-1 derivative for the treatment of metabolic syndrome and related diseases and disorders
  申请人：Novo Nordisk A/S

  公开号：US07202213B2

  公开（公告）日：2007-04-10

  The present invention relates to a pharmaceutical composition comprising a dual Peroxisome Proliferator-Activated Receptor-alpha/Peroxisome Proliferator-Activated Receptor-gama activator (PPAR-α/PPAR-γ) and a Glucagon Like Peptide-1 (GLP-1) derivative for treating, preventing and reducing the risk of developing Type 2 diabetes, insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders.

  本发明涉及一种药物组合物，包括一种双过氧化物酶体增殖物激活受体-α/过氧化物酶体增殖物激活受体-γ激动剂（PPAR-α/PPAR-γ）和一种类胰高血糖素样肽-1（GLP-1）衍生物，用于治疗、预防和降低发展2型糖尿病、胰岛素抵抗、血脂异常、肥胖症、高血压和其他相关疾病和疾病的风险。
• ALKYNYLSUBSTITUTED PROPIONIC ACID DERIVATIVES AND THEIR USE AGAINST DIABETES AND OBESITY
  申请人：Novo Nordisk A/S

  公开号：EP1254102A1

  公开（公告）日：2002-11-06
• US6569901B2
  申请人：——

  公开号：US6569901B2

  公开（公告）日：2003-05-27
• US7202213B2
  申请人：——

  公开号：US7202213B2

  公开（公告）日：2007-04-10