2-(5-Methyl-2-morpholin-4-yl-1,3-thiazol-4-yl)ethanol | 196810-39-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(5-Methyl-2-morpholin-4-yl-1,3-thiazol-4-yl)ethanol
• CAS: 196810-39-6
• 化学式: C₁₀H₁₆N₂O₂S
• 分子量: 228.315
• InChiKey: OQSBRFVSHXFIRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  73.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5-Methyl-2-morpholin-4-yl-1,3-thiazol-4-yl)ethanol 在 4-二甲氨基吡啶 、 TEA 、 caesium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-{2-(Isopropoxycarbonylamino-methyl)-4-[2-(5-methyl-2-morpholin-4-yl-thiazol-4-yl)-ethoxy]-phenyl}-propionic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands

  摘要：

  PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.011
• 作为产物：
  描述：

  4-吗啉硫代甲酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 61.0h， 生成 2-(5-Methyl-2-morpholin-4-yl-1,3-thiazol-4-yl)ethanol
  参考文献：
  名称：

  N-(2-Benzoylphenyl)-l-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety

  摘要：

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-{2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.

  DOI：

  10.1021/jm980413z

文献信息

• Halogenobenzyl aminopropionic acid derivatives
  申请人：——

  公开号：US20040102439A1

  公开（公告）日：2004-05-27

  A halogenobenzylaminopropionic acid derivative represented by the following formula (1): 1 or a pharmaceutically acceptable salt of the derivative, and a drug containing the same as an active ingredient for treating diabetes, hyperlipidemia, or similar pathological conditions.

  由以下公式（1）表示的卤代苯甲基氨基丙酸衍生物，或者该衍生物的药用盐，以及包含其作为活性成分的药物，用于治疗糖尿病、高脂血症或类似病理条件。
• HALOGENOBENZYL AMINOPROPIONIC ACID DERIVATIVES
  申请人：Toaeiyo Ltd.

  公开号：EP1466909A1

  公开（公告）日：2004-10-13

  A halogenobenzylaminopropionic acid derivative represented by the following formula (1): or a pharmaceutically acceptable salt of the derivative, and a drug containing the same as an active ingredient for treating diabetes, hyperlipidemia, or similar pathological conditions.

  由下式(1)代表的卤代苄基氨基丙酸衍生物： 或该衍生物的药学上可接受的盐，以及含有该衍生物作为活性成分的用于治疗糖尿病、高脂血症或类似病症的药物。
• US6933309B2
  申请人：——

  公开号：US6933309B2

  公开（公告）日：2005-08-23
• <i>N</i>-(2-Benzoylphenyl)-<scp>l</scp>-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety
  作者：Jon L. Collins、Steven G. Blanchard、G. Evan Boswell、Paul S. Charifson、Jeff E. Cobb、Brad R. Henke、Emily A. Hull-Ryde、Wieslaw M. Kazmierski、Debra H. Lake、Lisa M. Leesnitzer、Jürgen Lehmann、James M. Lenhard、Lisa A. Orband-Miller、Yolanda Gray-Nunez、Derek J. Parks、Kelli D. Plunkett、Wei-Qin Tong

  DOI：10.1021/jm980413z

  日期：1998.12.1

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.
• Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands
  作者：Alan M. Warshawsky、Charles A. Alt、Joseph T. Brozinick、Allen R. Harkness、Eric D. Hawkins、James R. Henry、Donald P. Matthews、Anne R. Miller、Elizabeth A. Misener、Chahrzad Montrose-Rafizadeh、Gary A. Rhodes、Quanrong Shen、Jennifer A. Vance、Uko E. Udodong、Minmin Wang、Tony Y. Zhang、Richard W. Zink

  DOI：10.1016/j.bmcl.2006.09.011

  日期：2006.12

  PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes. (c) 2006 Elsevier Ltd. All rights reserved.