ethyl 2-benzoyl-4,4-bis(diethoxyphosphoryl)-butyrate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-benzoyl-4,4-bis(diethoxyphosphoryl)-butyrate
• 英文别名: (3-Benzoyl-4-ethoxy4-oxobutylidene)bisphosphonic acid tetraethyl ester；Ethyl 2-benzoyl-4,4-bis(diethoxyphosphoryl)butanoate
• 化学式: C₂₁H₃₄O₉P₂
• 分子量: 492.443
• InChiKey: RFMAKZPGBPWJPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1,1-双(二乙氧基磷酰基)乙烯 、 苯甲酰乙酸乙酯 在 (S)-(pyrrolidinemethyl)pyrrolidine 、 苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以53%的产率得到ethyl 2-benzoyl-4,4-bis(diethoxyphosphoryl)-butyrate
  参考文献：
  名称：

  已知具有生物活性的宝石双膦酸盐手性结构类似物合成中的烯胺催化

  摘要：

  描述了手性 γ-酮双膦酸盐的合成。由 0.1 mol 当量催化的环酮与乙烯基双膦酸盐的迈克尔加成。(S)-(+)-1-(2-吡咯烷基)吡咯烷和苯甲酸以高达86%的产率、dr (cis/trans) > 1:99和高达99%的ee得到产物。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

  DOI：

  10.1002/ejoc.200800170

文献信息

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

  公开号：EP0544812A1

  公开（公告）日：1993-06-09
• US5412141A
  申请人：——

  公开号：US5412141A

  公开（公告）日：1995-05-02
• US5602115A
  申请人：——

  公开号：US5602115A

  公开（公告）日：1997-02-11
• [EN] BISPHOSPHONIC ACID DERIVATIVES AS ANTI-ARTHRITIC AGENTS
  申请人：THE UPJOHN COMPANY

  公开号：WO1992003451A1

  公开（公告）日：1992-03-05

  (EN) The bisphosphonates of formula (III): R2-X-(CW)m1-CR3R4-CH2-CM[PO-(OR1)2]2 bicyclic bisphosphonates (V), and cyclic bisphosphonates (VII) are useful as anti-arthritic agents and do not have the side effects of anti-arthritic agents which are prostaglandin synthetase inhibitors.(FR) Les bisphosphonates de la formule (III): R2-X(CW)m1-CR3R4-CH2-CM[PO-(OR1)2]2, des bisphosphonates bicycliques (IV), ainsi que des bisphosphonates cycliques (VII) sont utiles comme agents anti-arthritiques et ne présentent pas les effets secondaires d'agents anti-arthritiques qui constituent des inhibiteurs de synthétase de prostaglandine.