[2-(2-Oxo-3-phenylcyclohexyl)ethylidene]bisphosphonic acid tetraethyl ester

• 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: [2-(2-Oxo-3-phenylcyclohexyl)ethylidene]bisphosphonic acid tetraethyl ester
• 英文别名: 2-[2,2-Bis(diethoxyphosphoryl)ethyl]-6-phenylcyclohexan-1-one
• 化学式: C₂₂H₃₆O₇P₂
• 分子量: 474.471
• InChiKey: BCDMRAKUMQFMLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 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：

  2-苯基环己酮 、 1,1-双(二乙氧基磷酰基)乙烯 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56%的产率得到[2-(2-Oxo-3-phenylcyclohexyl)ethylidene]bisphosphonic acid tetraethyl ester
  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

• BISPHOSPHONIC ACID DERIVATIVES AS ANTI-ARTHRITIC AGENTS
  申请人：THE UPJOHN COMPANY

  公开号：EP0544812B1

  公开（公告）日：1995-04-05
• 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.