3-(4-benzyloxy-phenyl)-2-ethoxy-acrylic acid ethyl ester | 222835-03-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-benzyloxy-phenyl)-2-ethoxy-acrylic acid ethyl ester
• 英文别名: 3-(4-benzyloxyphenyl)-2-ethoxyacrylic acid ethyl ester；ethyl E/Z-3-(4-benzyloxyphenyl)-2-ethoxyacrylate；3-(4-(benzyloxy)phenyl)-2-ethoxy acrylic acid ethyl ester；3-(4-(benzyloxy)phenyl)-2-ethoxyacrylic acid ethyl ester；Ethyl 3-[4-(benzyloxy)phenyl]-2-ethoxyprop-2-enoate；ethyl 2-ethoxy-3-(4-phenylmethoxyphenyl)prop-2-enoate
• CAS: 222835-03-2
• 化学式: C₂₀H₂₂O₄
• 分子量: 326.392
• InChiKey: WCRKVPDIOHFYAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  3-(4-benzyloxy-phenyl)-2-ethoxy-acrylic acid ethyl ester 在 palladium on activated charcoal sodium hydroxide 、 氯化亚砜 、 phosphate buffer 、 Pectinex Ultra SP-L enzyme 、 氢气 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 82.0h， 生成 ragaglitazar
  参考文献：
  名称：

  Synthesis and Biological and Structural Characterization of the Dual-Acting Peroxisome Proliferator-Activated Receptor α/γ Agonist Ragaglitazar

  摘要：

  A new and improved synthesis of the peroxisome proliferator-activated receptor (PPAR) agonist ragaglitazar applicable for large-scale preparation has been developed. The convergent synthetic procedure was based on a novel enzymatic kinetic resolution step. The conformation of ragaglitazar bound to the hPPARgamma receptor was quite different compared to the single-crystal structures of the L-arginine salt of ragaglitazar. In particular, the phenoxazine ring system had varying orientations. Ragaglitazar had high affinity for the hPPARalpha and -gamma receptors with IC50 values of 0.98 and 0.092 muM, respectively. The lack of hPPARdelta activity could be explained by the absence of binding in the tail-up pocket in the hPPARdelta receptor, in contrast to the hPPARdelta agonist GW2433, which was able to bind in both the tail-up and tail-down pockets of the receptor.

  DOI：

  10.1021/jm021027r
• 作为产物：
  描述：

  2,2-二乙氧基乙酸乙酯 在 potassium tert-butylate 、 碘 、 乙酰氯 作用下， 以 甲苯 为溶剂， 生成 3-(4-benzyloxy-phenyl)-2-ethoxy-acrylic acid ethyl ester
  参考文献：
  名称：

  Process Development on the Enantioselective Enzymatic Hydrolysis of S-Ethyl 2-Ethoxy-3-(4-hydroxyphenyl)propanoate

  摘要：

  A novel biocatalytic approach for the large-scale production of S-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid S-1 from its racemic ethylester rac-2 by enantioselective hydrolysis has been developed. S-1 is an important building block in the synthesis of PPARalpha and -gamma agonists such as Ragaglitazar [NNC 61-0029 ((-)DRF2725)]. The development history comprises enzyme screening, biocatalyst and process optimization, and scale-up to pilot plant. The project was thereby highly interdisciplinary by combining biotechnology and chemistry technologies. The final process was successfully run on a 44-kg pilot scale in 43-48% yields and with high enantiomeric purities (98.4-99.6% ee).

  DOI：

  10.1021/op0256035

文献信息

• Design, synthesis, and structure–activity relationship of carbamate-tethered aryl propanoic acids as novel PPARα/γ dual agonists
  作者：Nam-Jung Kim、Kwang-Ok Lee、Bon-Woong Koo、Funan Li、Ja-Kyung Yoo、Hyun-Ju Park、Kyung-Hoon Min、Joong In Lim、Mi Kyung Kim、Jin-Kwan Kim、Young-Ger Suh

  DOI：10.1016/j.bmcl.2007.04.057

  日期：2007.7

  dual agonists, which show excellent agonistic activity in PPARalpha/gamma transactivation assay. In particular, (R)-9d was identified as a potent PPARalpha/gamma dual agonist with EC(50)s of 0.377 microM in PPARalpha and 0.136 microM in PPARgamma, respectively. Interestingly, the structure-activity relationship revealed that the stereochemistry of the identified PPARalpha/gamma dual agonists significantly

  我们开发了新型的PPARalpha /γ双激动剂，在PPARalpha /γ反式激活试验中显示出极好的激动活性。特别地，（R）-9d被确定为有效的PPARalpha /γ双重激动剂，其EC（50）在PPARalpha中为0.377 microM，在PPARgamma中为0.136 microM。有趣的是，结构-活性关系揭示了所鉴定的PPARα/γ双重激动剂的立体化学显着影响它们在PPARα中的激动活性，而不是在PPARγ中。
• NOVEL PHENYLPROPIONIC ACID DERIVATIVES AS PEROXISOME PROLIFERATOR-ACTIVATED GAMMA RECEPTOR MODULATORS, METHOD OF THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：Moon Ho-Sang

  公开号：US20100063041A1

  公开（公告）日：2010-03-11

  The present invention provides a novel phenylpropionic acid derivative and a PPAR-γ modulator comprising the same as an active ingredient. The phenylpropionic acid derivative of the present invention has modulatory action on function of PPAR-γ and then exhibits hypoglycemic, hypolipidemic and insulin resistance-reducing effects on PPAR-mediated diseases or disorders. Therefore, the present invention is prophylactically or therapeutically effective for diabetes and metabolic diseases.

  本发明提供了一种新型苯丙酸衍生物，以及包含该衍生物作为活性成分的PPAR-γ调节剂。本发明的苯丙酸衍生物对PPAR-γ的功能具有调节作用，从而在PPAR介导的疾病或紊乱中表现出降糖、降脂和减少胰岛素抵抗的效果。因此，本发明在预防或治疗糖尿病和代谢性疾病方面具有预防或治疗效果。
• [EN] AMIDE LINKER PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RECEPTEUR ACTIVE DE LA PROLIFERATION DES PEROXISOMES A LIEUR AMIDE
  申请人：LILLY CO ELI

  公开号：WO2004000789A1

  公开（公告）日：2003-12-31

  The present invention is directed to compounds, compositions, and use of compounds the structural Formula (I).

  本发明涉及结构式(I)的化合物、组合物及其使用。
• 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。
• [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。