ethyl 2-(2,2-diphenylacetoxy)-3-oxobutanoate | 1434871-32-5

• 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: ethyl 2-(2,2-diphenylacetoxy)-3-oxobutanoate
• 英文别名: Ethyl 2-(2,2-diphenylacetoxy)-3-oxobutanoate；ethyl 2-(2,2-diphenylacetyl)oxy-3-oxobutanoate
• CAS: 1434871-32-5
• 化学式: C₂₀H₂₀O₅
• 分子量: 340.376
• InChiKey: QMMSLPIZUWDWJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 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：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(2,2-diphenylacetoxy)-3-oxobutanoate 在 ammonium acetate 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Potent Heterocyclic Ligands for Human Complement C3a Receptor

  摘要：

  The G-protein coupled receptor (C3aR) for human inflammatory protein complement C3a is an important component of immune, inflammatory, and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist (IC50 mu M), was transformed here into potent agonists (EC50 nM) of human macrophages (Ca2+ release in HMDM) by incorporating aromatic heterocycles. Antagonists were also identified. A linear correlation between binding affinity for C3aR and calculated hydrogen-bond interaction energy of the heteroatom indicated that its hydrogen-bonding capacity influenced ligand affinity and function mediated by C3aR. Hydrogen-bond accepting heterocycles (e.g., imidazole) conferred the highest affinity and agonist potency (e.g., 21, EC50 24 nM, Ca2+, HMDM) with comparable efficacy and immunostimulatory activity as that of C3a in activating human macrophages (Ca2+, IL1 beta, TNF alpha, CCL3). These potent and selective modulators of C3aR, inactivated by a C3aR antagonist, are stable C3a surrogates for interrogating roles for C3aR in physiology and disease.

  DOI：

  10.1021/jm500956p
• 作为产物：
  描述：

  2,2-二苯基乙酸 、 2-氯乙酰乙酸乙酯 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 以98%的产率得到ethyl 2-(2,2-diphenylacetoxy)-3-oxobutanoate
  参考文献：
  名称：

  立体电子效应决定杂环酰胺的分子构象和生物学功能

  摘要：

  由于杂原子施加的立体电子效应，与酰胺相邻的杂环可以对分子构象产生重要影响。通过比较低能量构象（从头计算 MP2 和 DFT 计算）、电荷分布、偶极矩和支持一般原理的已知晶体结构，咪唑和噻唑酰胺显示了这一点。将杂原子从氮转换为硫改变了酰胺构象，产生了不同的三维静电表面。差异归因于不同的偶极子和轨道排列，并在调节人巨噬细胞上炎症蛋白补体 C3a 的 G 蛋白偶联受体方面显着地转化为相反的激动剂与拮抗剂功能。通过使用稠合双环锁定酰胺构象，证实了杂原子的影响。这些发现表明杂环的立体电子效应调节分子构象，并可以赋予截然不同的生物学特性。

  DOI：

  10.1021/ja506518t

文献信息

• [EN] MODULATORS OF C3A RECEPTORS<br/>[FR] MODULATEURS DES RÉCEPTEURS C3A
  申请人：UNIV QUEENSLAND

  公开号：WO2013067578A1

  公开（公告）日：2013-05-16

  Heterocyclic compounds that modulate C3a receptors and their use in the treatment or prevention of inflammatory diseases, infectious diseases, cancers, metabolic disorders, obesity, type 2 diabetes, metabolic syndrome and associated cardiovascular diseases are described. The use of the compounds in stimulating or suppressing an immune response is also described together with pharmaceutical compositions comprising the compounds or their pharmaceutically acceptable salts.

  描述了调节C3a受体的杂环化合物及其在治疗或预防炎症性疾病、传染病、癌症、代谢紊乱、肥胖、2型糖尿病、代谢综合征以及相关心血管疾病中的用途。还描述了这些化合物在刺激或抑制免疫反应中的用途，以及包含这些化合物或其药用可接受盐的制药组合物。
• MODULATORS OF C3A RECEPTORS
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：US20140302069A1

  公开（公告）日：2014-10-09

  Heterocyclic compounds that modulate C3a receptors and their use in the treatment or prevention of inflammatory diseases, infectious diseases, cancers, metabolic disorders, obesity, type 2 diabetes, metabolic syndrome and associated cardiovascular diseases are described. The use of the compounds in stimulating or suppressing an immune response is also described together with pharmaceutical compositions comprising the compounds or their pharmaceutically acceptable salts.

  本文描述了调节C3a受体的杂环化合物及其在治疗或预防炎症性疾病、传染性疾病、癌症、代谢性疾病、肥胖症、2型糖尿病、代谢综合征及相关心血管疾病中的应用。本文还描述了利用这些化合物刺激或抑制免疫反应的应用，以及包括这些化合物或其药学上可接受的盐的制药组合物。
• US9586914B2
  申请人：——

  公开号：US9586914B2

  公开（公告）日：2017-03-07
• Potent Heterocyclic Ligands for Human Complement C3a Receptor
  作者：Robert C. Reid、Mei-Kwan Yau、Ranee Singh、Johan K. Hamidon、Junxian Lim、Martin J. Stoermer、David P. Fairlie

  DOI：10.1021/jm500956p

  日期：2014.10.23

  The G-protein coupled receptor (C3aR) for human inflammatory protein complement C3a is an important component of immune, inflammatory, and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist (IC50 mu M), was transformed here into potent agonists (EC50 nM) of human macrophages (Ca2+ release in HMDM) by incorporating aromatic heterocycles. Antagonists were also identified. A linear correlation between binding affinity for C3aR and calculated hydrogen-bond interaction energy of the heteroatom indicated that its hydrogen-bonding capacity influenced ligand affinity and function mediated by C3aR. Hydrogen-bond accepting heterocycles (e.g., imidazole) conferred the highest affinity and agonist potency (e.g., 21, EC50 24 nM, Ca2+, HMDM) with comparable efficacy and immunostimulatory activity as that of C3a in activating human macrophages (Ca2+, IL1 beta, TNF alpha, CCL3). These potent and selective modulators of C3aR, inactivated by a C3aR antagonist, are stable C3a surrogates for interrogating roles for C3aR in physiology and disease.
• Stereoelectronic Effects Dictate Molecular Conformation and Biological Function of Heterocyclic Amides
  作者：Robert C. Reid、Mei-Kwan Yau、Ranee Singh、Junxian Lim、David P. Fairlie

  DOI：10.1021/ja506518t

  日期：2014.8.27

  on molecular conformation due to stereoelectronic effects exerted by the heteroatom. This was shown for imidazole- and thiazole-amides by comparing low energy conformations (ab initio MP2 and DFT calculations), charge distribution, dipole moments, and known crystal structures which support a general principle. Switching a heteroatom from nitrogen to sulfur altered the amide conformation, producing different

  由于杂原子施加的立体电子效应，与酰胺相邻的杂环可以对分子构象产生重要影响。通过比较低能量构象（从头计算 MP2 和 DFT 计算）、电荷分布、偶极矩和支持一般原理的已知晶体结构，咪唑和噻唑酰胺显示了这一点。将杂原子从氮转换为硫改变了酰胺构象，产生了不同的三维静电表面。差异归因于不同的偶极子和轨道排列，并在调节人巨噬细胞上炎症蛋白补体 C3a 的 G 蛋白偶联受体方面显着地转化为相反的激动剂与拮抗剂功能。通过使用稠合双环锁定酰胺构象，证实了杂原子的影响。这些发现表明杂环的立体电子效应调节分子构象，并可以赋予截然不同的生物学特性。