rac-3-{4-[2-Amino-6-(4-benzyl-piperazin-1-yl)-pyrimidin-4-yloxy]-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester | 956223-21-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: rac-3-{4-[2-Amino-6-(4-benzyl-piperazin-1-yl)-pyrimidin-4-yloxy]-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester
• 英文别名: 3-{4-[2-Amino-6-(4-benzyl-piperazin-1-yl)-pyrimidin-4-yloxy]-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester；ethyl 3-[4-[2-amino-6-(4-benzylpiperazin-1-yl)pyrimidin-4-yl]oxyphenyl]-2-methyl-2-phenoxypropanoate
• CAS: 956223-21-5
• 化学式: C₃₃H₃₇N₅O₄
• 分子量: 567.688
• InChiKey: ZKXJWWUJKFFAEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  rac-3-{4-[2-Amino-6-(4-benzyl-piperazin-1-yl)-pyrimidin-4-yloxy]-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester 在 3-{4-[2-amino-6-(4-benzylpiperazin-1-yl)pyrimidin-4-yloxy]phenyl}-2-methyl-2-phenoxypropionic acid 作用下， 以 四氢呋喃 、 potassium hydrate 为溶剂， 反应 20.0h， 生成 3-{4-[2-amino-6-(4-benzylpiperazin-1-yl)pyrimidin-4-yloxy]phenyl}-2-methyl-2-phenoxypropionic acid
  参考文献：
  名称：

  Pyrimidinyl-propionic acid derivatives and their use as PPAR agonists

  摘要：

  本发明揭示了结构式（I）的化合物，其对映体，外消旋体，药学上可接受的盐，溶剂合物或水合物，其中可变基团如下所定义，并且制备这种化合物的方法。这些化合物可用作PPARγ激动剂，通过激活与靶基因启动子区域内特定DNA响应元素相互作用的PPAR-RXR异源二聚体，特别在多囊肾和癌症的治疗和预防中有用。

  公开号：

  US08513233B2
• 作为产物：
  描述：

  4-(4-苄基哌嗪-1-基)-6-氯嘧啶-2-胺 、 3-(4-hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl ester 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以70%的产率得到rac-3-{4-[2-Amino-6-(4-benzyl-piperazin-1-yl)-pyrimidin-4-yloxy]-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester
  参考文献：
  名称：

  [EN] PYRIMIDINYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
  [FR] DÉRIVÉS DE L'ACIDE PYRIMIDINYLE PROPIONIQUE ET LEUR UTILISATION EN TANT QU'AGONISTES PPAR

  摘要：

  本发明揭示了结构式（I）的化合物，以及其对映体、消旋体、药用可接受的盐、溶剂合物或水合物，其中变量基团如定义内所述，以及制备这种化合物的方法。这些化合物可作为PPARγ激动剂使用，通过激活与靶基因启动子区域内特定DNA响应元件相互作用的PPAR-RXR异二聚体，在多囊肾和癌症的治疗和预防中特别有用。

  公开号：

  WO2009046606A1

文献信息

• [EN] PYRIMIDINYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS<br/>[FR] DÉRIVÉS DE L'ACIDE PYRIMIDINYLE PROPIONIQUE ET LEUR UTILISATION EN TANT QU'AGONISTES PPAR
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2009046606A1

  公开（公告）日：2009-04-16

  The present invention disclosed compounds of Structural Formula (I), and enantiomer, racemic body, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein variable groups are as defined within, as well as methods for preparing such compounds. The compounds are useful as PPARγ agonist, through activating PPAR-RXR heterodimers that intereacts with specific DNA response elements within promoter regions of target gene, particularly in the treatment and prevention of polycystic kidney and cancer.

  本发明揭示了结构式（I）的化合物，以及其对映体、消旋体、药用可接受的盐、溶剂合物或水合物，其中变量基团如定义内所述，以及制备这种化合物的方法。这些化合物可作为PPARγ激动剂使用，通过激活与靶基因启动子区域内特定DNA响应元件相互作用的PPAR-RXR异二聚体，在多囊肾和癌症的治疗和预防中特别有用。
• Discovery of novel dual functional agent as PPARγ agonist and 11β-HSD1 inhibitor for the treatment of diabetes
  作者：Yang-liang Ye、Zhou Zhou、Han-jun Zou、Yu Shen、Ti-fei Xu、Jing Tang、Hua-zhong Yin、Min-li Chen、Ying Leng、Jian-hua Shen

  DOI：10.1016/j.bmc.2009.05.082

  日期：2009.8

  PPAR gamma and 11 beta-HSD1 are attractive therapeutic targets for type 2 diabetes. However, PPAR gamma agonists induce adipogenesis, which causes the side effect of weight gain, whereas 11 beta-HSD1 inhibitors prevent adipogenesis and may be beneficial for the treatment of obesity in diabetic patients. For the first time, we designed, synthesized a series of alpha-aryloxy-alpha-methylhydrocinnamic acids as dual functional agents which activate PPAR gamma and inhibit 11 beta-HSD1 simultaneously. The compound 11e exhibited the most potent inhibitory activity compared to that of the lead compound 2, with PPAR gamma (EC50 = 6.76 mu M) and 11 beta-HSD1 (IC50 = 0.76 mu M) in vitro. Molecular modeling study for compound 11e was also presented. Compound 11e showed excellent efficacy for lowering glucose, triglycerides, body fat, in well established mice and rats models of diabetes and obesity and had a favorable ADME profile. (C) 2009 Elsevier Ltd. All rights reserved.
• US8513233B2
  申请人：——

  公开号：US8513233B2

  公开（公告）日：2013-08-20
• PYRIMIDINYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
  申请人：Shen Jianhua

  公开号：US20100240636A1

  公开（公告）日：2010-09-23

  The present invention disclosed compounds of Structural Formula (I), and enantiomer, racemic body, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein variable groups are as defined within, as well as methods for preparing such compounds. The compounds are useful as PPARγ agonist, through activating PPAR-RXR heterodimers that intereacts with specific DNA response elements within promoter regions of target gene, particularly in the treatment and prevention of polycystic kidney and cancer.

  本发明揭示了结构式（I）的化合物，以及其对映体、消旋体、药用可接受的盐、溶剂合物或水合物，其中变量基团如定义所述，以及制备这种化合物的方法。这些化合物可用作PPARγ激动剂，通过激活与靶基因启动子区域内特定DNA响应元素相互作用的PPAR-RXR异源二聚体，在多囊肾和癌症的治疗和预防中特别有用。
• Pyrimidinyl-propionic acid derivatives and their use as PPAR agonists
  申请人：Shen Jianhua

  公开号：US08513233B2

  公开（公告）日：2013-08-20

  The present invention disclosed compounds of Structural Formula (I), and enantiomer, racemic body, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein variable groups are as defined within, as well as methods for preparing such compounds. The compounds are useful as PPARγ agonist, through activating PPAR-RXR heterodimers that interacts with specific DNA response elements within promoter regions of target gene, particularly in the treatment and prevention of polycystic kidney and cancer.

  本发明揭示了结构式（I）的化合物，其对映体，外消旋体，药学上可接受的盐，溶剂合物或水合物，其中可变基团如下所定义，并且制备这种化合物的方法。这些化合物可用作PPARγ激动剂，通过激活与靶基因启动子区域内特定DNA响应元素相互作用的PPAR-RXR异源二聚体，特别在多囊肾和癌症的治疗和预防中有用。