ethyl 2-(diethoxyphosphoryl)-2-(2,2,2-trifluoroethoxy)acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: ethyl 2-(diethoxyphosphoryl)-2-(2,2,2-trifluoroethoxy)acetate
• 英文别名: ethyl 2,2,2-trifluoroethoxy-2-(diethylphosphono)acetate；2-(trifluoroethoxy)-2-diethylphosphonoacetate；Ethyl 2-diethoxyphosphoryl-2-(2,2,2-trifluoroethoxy)acetate
• 化学式: C₁₀H₁₈F₃O₆P
• 分子量: 322.218
• InChiKey: DNMMVZQFPGBBMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  、 ethyl 2-(diethoxyphosphoryl)-2-(2,2,2-trifluoroethoxy)acetate 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以82%的产率得到ethyl (2Z,6E)-6-methyl-9-(2-methyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)-2-(2,2,2-trifluoroethoxy)nona-2,6-dienoate
  参考文献：
  名称：

  Synthesis of 2-Prenylated Alkoxylated Benzopyrans by Horner–Wadsworth–Emmons Olefination with PPARα/γ Agonist Activity

  摘要：

  DOI：

  10.1021/acsmedchemlett.1c00400
• 作为产物：
  描述：

  磷酰基乙酸三乙酯 在 dirhodium tetraacetate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 21.0h， 生成 ethyl 2-(diethoxyphosphoryl)-2-(2,2,2-trifluoroethoxy)acetate
  参考文献：
  名称：

  Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression

  摘要：

  A series of benzothiazol-2-one containing alpha-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPAR gamma agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPAR gamma agonist activity (Emax = 98%, EC50 = 200 nM), SIRTI enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGKI expression. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.006

文献信息

• [EN] INDOLE COMPOUNDS<br/>[FR] COMPOSÉS INDOLE
  申请人：THIA MEDICA AS

  公开号：WO2010011147A1

  公开（公告）日：2010-01-28

  Novel indole compounds which interact with peroxisome proliferator-activated receptors (PPARs) are disclosed. The compounds have an influence on metabolic diseases, obesity and diabetes.

  揭示了与过氧化物酶体增殖物激活受体（PPARs）相互作用的新型吲哚化合物。这些化合物对代谢性疾病、肥胖和糖尿病有影响。
• Synthesis of novel PPARα/γ dual agonists as potential drugs for the treatment of the metabolic syndrome and diabetes type II designed using a new de novo design program<scp>protobuild</scp>
  作者：Yushma Bhurruth-Alcor、Therese Røst、Michael R. Jorgensen、Christos Kontogiorgis、Jon Skorve、Robert G. Cooper、Joseph M. Sheridan、William D. O. Hamilton、Jonathan R. Heal、Rolf K. Berge、Andrew D. Miller

  DOI：10.1039/c0ob00146e

  日期：——

  Peroxisome proliferator activated receptors (PPARs) have been shown to have critical roles in fatty acid oxidation, triglyceride synthesis, and lipid metabolism - making them an important target in drug discovery. Here we describe the in silico design, synthesis and in vitro characterisation of a novel series of 2,5-disubstituted indoles as PPARα/γ dual agonists. PPAR activation assays are performed with known agonists diazabenzene (WY14.643), aminopyridine (BRL49653) and bisaryl (L165.041), as positive controls. All the indole compounds synthesized are found to be active PPARα and PPARγ agonists, with particular efficacy from those with 2-naphthylmethyl substitution. This is a useful demonstration of a new de novo design methodology implemented by the PROTOBUILD program and its ability to rapidly produce novel modulators for a well characterized drug target.

  过氧化物酶体增殖物激活受体（PPARs）在脂肪酸氧化、甘油三酯合成和脂质代谢中具有关键作用，使其成为药物发现的重要靶点。本文报道了通过计算设计、合成和体外表征一系列新型2,5-二取代吲哚类化合物作为PPARα/γ双激动剂的方法。使用已知激动剂二氮苯并噻吩（WY14,643）、氨基吡啶（BRL49653）和二芳基（L165,041）作为阳性对照进行PPAR激活试验。所有合成的吲哚化合物均显示出PPARα和PPARγ激动活性，其中2-萘甲基取代的吲哚化合物具有特别高的效能。这一成果展示了通过PROTOBUILD程序实现的新颖从头设计方法的有用性及其快速产生针对已知药物靶点的新型调节剂的能力。
• Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects
  作者：Carlos Villarroel-Vicente、Ainhoa García、Khamis Zibar、María Ayelén Schiel、Jordi Ferri、Nathalie Hennuyer、Ricardo D. Enriz、Bart Staels、Diego Cortes、Nuria Cabedo

  DOI：10.1016/j.bmcl.2024.129770

  日期：2024.7

  We have previously reported the total synthesis and structure–activity relationships (SAR) of 2-prenylated benzopyrans with PPAR agonist activity. Herein, we have described the synthesis and PPAR activity of 2-prenylated benzopyrans and 2-prenylated quinolines. The benzopyran nucleus was generated via enamine-catalyzed Kabbe condensation, and the quinoline nucleus via Friedländer condensation. Results

  我们之前报道了具有 PPAR 激动剂活性的 2-异戊二烯化苯并吡喃的全合成和构效关系 (SAR)。在此，我们描述了 2-异戊二烯化苯并吡喃和 2-异戊二烯化喹啉的合成和 PPAR 活性。苯并吡喃核通过烯胺催化的卡贝缩合生成，喹啉核通过弗里德兰德缩合生成。结果表明，带有 γ,δ-不饱和酯的苯并吡喃 () 和喹啉 () 衍生物均表现出泛 PPAR 激动作用。它们是 PPARα 完全激动剂，但对 PPARγ 和 PPARβ/δ 激活表现出不同的偏好。值得注意的是，喹啉表现出完全的 hPPARα 激活（是 WY-14,643 的 2 倍）、弱的 PPARβ/δ 和部分 PPARγ 激活。此外，喹啉通过减少 LPS 诱导的 和 的表达，对巨噬细胞显示出抗炎作用。因此，它成为一种一流的有希望的热门化合物，用于开发旨在治疗代谢综合征、代谢功能障碍相关脂肪肝病 (MAFLD) 及其相关心血管合并症的潜在疗法。
• Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression
  作者：Celine Pirat、Catherine Dacquet、Veronique Leclerc、Nathalie Hennuyer、Monique Beucher-Gaudin、Ghislaine Zanirato、Anne Géant、Bart Staels、Alain Ktorza、Amaury Farce、Daniel-Henri Caignard、Pascal Berthelot、Nicolas Lebegue

  DOI：10.1016/j.ejmech.2017.06.006

  日期：2017.9

  A series of benzothiazol-2-one containing alpha-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPAR gamma agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPAR gamma agonist activity (Emax = 98%, EC50 = 200 nM), SIRTI enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGKI expression. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Non-thiazolidinedione antihyperglycaemic agents. Part 4: Synthesis of (±)-, (R)-(+)- and (S)-(−)-enantiomers of 2-oxy-3-arylpropanoic acids
  作者：David Haigh、Helen C Birrell、Barrie C.C Cantello、Richard M Hindley、Anantha Ramaswamy、Harshad K Rami、Nicola C Stevens

  DOI：10.1016/s0957-4166(99)00104-4

  日期：1999.4

  The synthesis of a new series of potent 2-oxy-3-arylpropanoic acid antihyperglycaemic agents in both racemic and non-racemic form is described. Resolution of racemic acids 1 is accomplished via amide formation with either (S)-2-phenylglycinol or (S)-4-benzyloxazolidin-2-one as complementary resolving agents. (C) 1999 Elsevier Science Ltd. All rights reserved.