(2Z)-4,4-二乙氧基-2-(乙氧基亚甲基)-3-氧代丁酸乙酯 | 40995-61-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: (2Z)-4,4-二乙氧基-2-(乙氧基亚甲基)-3-氧代丁酸乙酯
• 英文名称: 2-diethoxyacetyl-3-ethoxy-acrylic acid ethyl ester
• 英文别名: ethyl 4,4-diethoxy-2-(ethoxymethylene)-3-oxobutyrate；Ethyl 4,4-diethoxy-2-(ethoxymethylidene)-3-oxobutanoate
• CAS: 40995-61-7
• 化学式: C₁₃H₂₂O₆
• 分子量: 274.314
• InChiKey: CJDBTRBKLAYPCF-UHFFFAOYSA-N

物化性质

• 沸点：
  335.8±42.0 °C(Predicted)
• 密度：
  1.068±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  (2Z)-4,4-二乙氧基-2-(乙氧基亚甲基)-3-氧代丁酸乙酯 在 羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 4-Carbaethoxy-5-(formyldiaethylacetal)-isoxazol
  参考文献：
  名称：

  Synthese de formyl-3 carbethoxy-4 et carbethoxy-4 formyl-5 pyrazoles N1-substitues

  摘要：

  DOI：

  10.1016/s0040-4020(01)93313-7
• 作为产物：
  描述：

  4,4-二乙氧基-3-氧代丁酸乙酯 、 原甲酸三乙酯 在 乙酸酐 作用下， 生成 (2Z)-4,4-二乙氧基-2-(乙氧基亚甲基)-3-氧代丁酸乙酯
  参考文献：
  名称：

  Part 2: Structure–activity relationship (SAR) investigations of fused pyrazoles as potent, selective and orally available inhibitors of p38α mitogen-activated protein kinase

  摘要：

  A novel class of pyrazolopyridazine p38 alpha mitogen-activated protein kinase (MAPK) inhibitors is disclosed. A structure activity relationship (SAR) investigation was conducted driven by the ability of these compounds to inhibit the p38a enzyme, the secretion of TNF alpha in a LPS-challenged THP1 cell line and TNF alpha-induced production of IL-8 in the presence of 50% human whole blood (hWB). This study resulted in the discovery of several inhibitors with IC50 values in the single-digit nanomolar range in hWB. Further investigation of the pharmacokinetic profiles of these lead compounds led to the identification of three potent and orally bioavailable p38 alpha inhibitors 2h, 2m, and 13h. Inhibitor 2m was found to be highly selective for p38 alpha/beta over a panel of 402 other kinases in Ambit screening, and was highly efficacious in vivo in the inhibition of TNF alpha production in LPS-stimulated Lewis rats with an ED50 of ca. 0.08 mg/kg. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.059

文献信息

• Battesti,P. et al., Bulletin de la Societe Chimique de France, 1974, p. 2221 - 2224
  作者：Battesti,P. et al.

  DOI：——

  日期：——
• Part 2: Structure–activity relationship (SAR) investigations of fused pyrazoles as potent, selective and orally available inhibitors of p38α mitogen-activated protein kinase
  作者：Ryan P. Wurz、Liping H. Pettus、Bradley Henkle、Lisa Sherman、Matthew Plant、Kent Miner、Helen J. McBride、Lu Min Wong、Christiaan J.M. Saris、Matthew R. Lee、Samer Chmait、Christopher Mohr、Faye Hsieh、Andrew S. Tasker

  DOI：10.1016/j.bmcl.2010.01.059

  日期：2010.3

  A novel class of pyrazolopyridazine p38 alpha mitogen-activated protein kinase (MAPK) inhibitors is disclosed. A structure activity relationship (SAR) investigation was conducted driven by the ability of these compounds to inhibit the p38a enzyme, the secretion of TNF alpha in a LPS-challenged THP1 cell line and TNF alpha-induced production of IL-8 in the presence of 50% human whole blood (hWB). This study resulted in the discovery of several inhibitors with IC50 values in the single-digit nanomolar range in hWB. Further investigation of the pharmacokinetic profiles of these lead compounds led to the identification of three potent and orally bioavailable p38 alpha inhibitors 2h, 2m, and 13h. Inhibitor 2m was found to be highly selective for p38 alpha/beta over a panel of 402 other kinases in Ambit screening, and was highly efficacious in vivo in the inhibition of TNF alpha production in LPS-stimulated Lewis rats with an ED50 of ca. 0.08 mg/kg. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthese de formyl-3 carbethoxy-4 et carbethoxy-4 formyl-5 pyrazoles N1-substitues
  作者：E. Bisagni、J.-D. Bourzat、J.-P. Marquet、J. André-Louisfert

  DOI：10.1016/s0040-4020(01)93313-7

  日期：1973.1