ethyl 2-methylene-4,4-diphenylbutanoate | 1227164-15-9

• 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-methylene-4,4-diphenylbutanoate
• 英文别名: ethyl 2-(2,2-diphenylethyl)acrylate；Ethyl 2-methylidene-4,4-diphenylbutanoate；ethyl 2-methylidene-4,4-diphenylbutanoate
• CAS: 1227164-15-9
• 化学式: C₁₉H₂₀O₂
• 分子量: 280.367
• InChiKey: JVCQRPVAOYJIMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 2-methylene-4,4-diphenylbutanoate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 为溶剂， 反应 30.33h， 生成 ((1R)-1-amino-3-phenylpropyl){2′-[((2″S)-1″-amino-4″-methyl-1″-oxopentan-2″-yl)carbamoyl]-4′,4′-diphenylbutyl}phosphinic acid
  参考文献：
  名称：

  Optimization and Structure–Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides

  摘要：

  The oxytocinase subfamily of M1 aminopeptidases, Consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously,demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P-1' and P-2' positions are Critical determinants in driving potency and selectivity. We identified low nanomolar inhibitors of ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude, respectively. Cellular analysis demonstrated that one of the compounds that is a selective IRAP inhibitor can reduce IRAP-dependent but not, ERAP1-dependent cross-presentation by dendritic cells with nanomolar efficacy. Our results encourage further preclinical development of phosphinic pseudotripeptides as regulators of adaptive immune responses.

  DOI：

  10.1021/acs.jmedchem.6b01031
• 作为产物：
  描述：

  5-(1-hydroxy-2,2-diphenylethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 24.0h， 生成 ethyl 2-methylene-4,4-diphenylbutanoate
  参考文献：
  名称：

  Optimization and Structure–Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides

  摘要：

  The oxytocinase subfamily of M1 aminopeptidases, Consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously,demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P-1' and P-2' positions are Critical determinants in driving potency and selectivity. We identified low nanomolar inhibitors of ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude, respectively. Cellular analysis demonstrated that one of the compounds that is a selective IRAP inhibitor can reduce IRAP-dependent but not, ERAP1-dependent cross-presentation by dendritic cells with nanomolar efficacy. Our results encourage further preclinical development of phosphinic pseudotripeptides as regulators of adaptive immune responses.

  DOI：

  10.1021/acs.jmedchem.6b01031

文献信息

• Large-Scale Preparation of Polyfunctional Benzylic Zinc Reagents by Direct Insertion of Zinc Dust into Benzylic Chlorides in the Presence of Lithium Chloride
  作者：Paul Knochel、Albrecht Metzger、Christian Argyo

  DOI：10.1055/s-0029-1217134

  日期：2010.3

  prepared by the direct insertion of commercially available zinc dust into the corresponding benzylic chlorides in the presence of stoichiometric amount of lithium chloride. These polyfunctional zinc organometallics react with various electrophiles leading to a broad range of functionalized products. insertion - zinc organometallics - zinc - benzylic zinc chlorides - lithium chloride

  通过在化学计量的氯化锂的存在下将可商购的锌粉直接插入相应的苄基氯化物中来制备高度官能化的苄基氯化锌。这些多官能锌有机金属化合物可与各种亲电试剂反应，从而产生多种官能化产物。 插入-有机金属锌-锌-苄基氯化锌-氯化锂
• Optimization and Structure–Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides
  作者：Paraskevi Kokkala、Anastasia Mpakali、Francois-Xavier Mauvais、Athanasios Papakyriakou、Ira Daskalaki、Ioanna Petropoulou、Sofia Kavvalou、Mirto Papathanasopoulou、Stefanos Agrotis、Theodora-Markisia Fonsou、Peter van Endert、Efstratios Stratikos、Dimitris Georgiadis

  DOI：10.1021/acs.jmedchem.6b01031

  日期：2016.10.13

  The oxytocinase subfamily of M1 aminopeptidases, Consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously,demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P-1' and P-2' positions are Critical determinants in driving potency and selectivity. We identified low nanomolar inhibitors of ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude, respectively. Cellular analysis demonstrated that one of the compounds that is a selective IRAP inhibitor can reduce IRAP-dependent but not, ERAP1-dependent cross-presentation by dendritic cells with nanomolar efficacy. Our results encourage further preclinical development of phosphinic pseudotripeptides as regulators of adaptive immune responses.