tetraethyl [2-(2',3'-dihydro-1'-oxoindene-2'-yl)ethylidene]bisphosphonate

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: tetraethyl [2-(2',3'-dihydro-1'-oxoindene-2'-yl)ethylidene]bisphosphonate
• 英文别名: 2-[2,2-Bis(diethoxyphosphoryl)ethyl]-2,3-dihydroinden-1-one
• 化学式: C₁₉H₃₀O₇P₂
• 分子量: 432.391
• InChiKey: GMPMFNCBLNRJEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1,1-双(二乙氧基磷酰基)乙烯 、 1-茚酮 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 以25%的产率得到tetraethyl [2-(2',3'-dihydro-1'-oxoindene-2'-yl)ethylidene]bisphosphonate
  参考文献：
  名称：

  Carbonyl-Containing Bisphosphonate Esters as Novel Antiinflammatory and Antiarthritic Agents

  摘要：

  A study of the decomposition of the pyrazoline bisphosphonate ester 2 identified 3 as the sole bisphosphonate component. Evaluation in a delayed-type hypersensitivity granuloma model of chronic inflammation in mice (DTH-GRA) showed 3 to be a potent inhibitor of granuloma formation (sc, 10 mg/kg, 45%), but in a murine model of antigen-induced arthritis (AIA), no significant inhibition was observed. As a result, new ketonic bisphosphonate tetraethyl esters were synthesized from vinylidenebisphosphonic acid tetraethyl ester 4 and activated carbonyl compounds in 13-84% yield. 6 significantly inhibited the pathology of both the DTH-GRA (sc, 25 mg/kg, 45%) and AIA models (sc, 25 mg/kg, 55%). Other compounds in the series were not as potent. Our results show that bisphosphonate ester 6 can inhibit the chronic inflammatory response associated with cutaneous granuloma formation and erosive arthritis.

  DOI：

  10.1021/jm00052a004

文献信息

• Synthesis of geminal bisphosphonates via organocatalyzed enantioselective Michael additions of cyclic ketones and 4-piperidones
  作者：Ana Maria Faísca Phillips、Maria Teresa Barros

  DOI：10.1039/c1ob06473h

  日期：——

  A Michael addition reaction of cyclic ketones and piperidones to a vinyl phosphonate is described. The reaction, catalyzed by chiral diamines, produced geminal γ-oxobisphosphonates in high yields (up to 92%) and very high ees (up to >99%). Disubstituted ketones gave drs of up to 8 : 92. The synthesis and characterization of several new compounds with potential biological activity is described.

  描述了环酮和哌啶酮的迈克尔加成反应成膦酸乙烯基酯。由手性二胺催化的反应以高产率（高达92％）和非常高的ee（高达> 99％）产生了双结晶的γ-氧代双膦酸酯。双取代的酮最多可得到8:92的drs。描述了几种具有潜在生物活性的新化合物的合成和表征。
• Carbonyl-Containing Bisphosphonate Esters as Novel Antiinflammatory and Antiarthritic Agents
  作者：Richard A. Nugent、Stephen T. Schlachter、Megan Murphy、Colin J. Dunn、Nigel D. Staite、Louise A. Galinet、Sharon K. Shields、Haiyan Wu、Danielle G. Aspar、Karen A. Richard

  DOI：10.1021/jm00052a004

  日期：1994.12

  A study of the decomposition of the pyrazoline bisphosphonate ester 2 identified 3 as the sole bisphosphonate component. Evaluation in a delayed-type hypersensitivity granuloma model of chronic inflammation in mice (DTH-GRA) showed 3 to be a potent inhibitor of granuloma formation (sc, 10 mg/kg, 45%), but in a murine model of antigen-induced arthritis (AIA), no significant inhibition was observed. As a result, new ketonic bisphosphonate tetraethyl esters were synthesized from vinylidenebisphosphonic acid tetraethyl ester 4 and activated carbonyl compounds in 13-84% yield. 6 significantly inhibited the pathology of both the DTH-GRA (sc, 25 mg/kg, 45%) and AIA models (sc, 25 mg/kg, 55%). Other compounds in the series were not as potent. Our results show that bisphosphonate ester 6 can inhibit the chronic inflammatory response associated with cutaneous granuloma formation and erosive arthritis.