2-(2-Dimethylamino-5-methyl-thiazol-4-yl)-ethanol | 196810-44-3

• 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-(2-Dimethylamino-5-methyl-thiazol-4-yl)-ethanol
• 英文别名: 2-[2-(Dimethylamino)-5-methyl-1,3-thiazol-4-yl]ethanol
• CAS: 196810-44-3
• 化学式: C₈H₁₄N₂OS
• 分子量: 186.278
• InChiKey: URZOKFUFYGIPQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-Dimethylamino-5-methyl-thiazol-4-yl)-ethanol 在 lithium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.5h， 生成 (S)-2-(2-Benzoyl-phenylamino)-3-{4-[2-(2-dimethylamino-5-methyl-thiazol-4-yl)-ethoxy]-phenyl}-propionic acid
  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
• 作为产物：
  描述：

  4-溴-3-氧代戊酸甲酯 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 61.0h， 生成 2-(2-Dimethylamino-5-methyl-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

• [EN] AMINOPIPERIDINES AND REALTED COMPOUNDS<br/>[FR] AMINOPIPÉRIDINES ET COMPOSÉS APPARENTÉS
  申请人：NEUROGEN CORP

  公开号：WO2008016811A2

  公开（公告）日：2008-02-07

  [EN] Aminopiperidines and related compounds of the formulas are provided: in which variables are described herein. Such compounds may be used to modulate MCH receptor activity in vivo or in vitro, and are particularly useful in the treatment of a variety of metabolic, feeding and sexual disorders in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such Iigands for detecting MCH receptors (e.g., receptor localization studies).
  [FR] L'invention concerne des aminopipéridines et des composés apparentés représentés par les formules dans lesquelles des variables sont décrites dans les présentes. De tels composés peuvent être utilisés pour moduler l'activité du récepteur MCH in vivo ou in vitro, et sont particulièrement utiles dans le traitement d'une diversité de troubles métaboliques, de l'alimentation et sexuels chez les êtres humains, les animaux de compagnie domestiqués et les animaux de bétail. L'invention concerne des compositions pharmaceutiques et des procédés pour traiter de tels troubles, ainsi que des procédés pour utiliser de tels ligands pour détecter les récepteurs MCH (par exemple, études de l'emplacement des récepteurs).