[3-Cyano-3-(2-pyridinyl)propylidene]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: [3-Cyano-3-(2-pyridinyl)propylidene]bisphosphonic acid tetraethyl ester
• 英文别名: 4,4-Bis(diethoxyphosphoryl)-2-pyridin-2-ylbutanenitrile
• 化学式: C₁₇H₂₈N₂O₆P₂
• 分子量: 418.367
• InChiKey: CJQNJVCKTNXRFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  三甲基溴硅烷 、 [3-Cyano-3-(2-pyridinyl)propylidene]bisphosphonic acid tetraethyl ester 以 氯仿 、 水 、 乙酸乙酯 为溶剂， 生成 (4-Cyano-3-(2-pyridinyl)butylidene)bisphosphonic acid
  参考文献：
  名称：

  Bisphosphonic acid derivatives as anti-arthritic agents

  摘要：

  公式（III）中的双膦酸盐R.sub.2 --X--(CW).sub.m1 --CR.sub.3 R.sub.4 --CH.sub.2 --CM[PO--(OR.sub.1).sub.2 ].sub.2（III），双环双膦酸盐（V），和环状双膦酸盐（VII）可用作抗关节炎药物，并且不具有前列腺素合成酶抑制剂的副作用。

  公开号：

  US05412141A1
• 作为产物：
  描述：

  2-吡啶乙腈 、 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48%的产率得到[3-Cyano-3-(2-pyridinyl)propylidene]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：EP0544812A1

  公开（公告）日：1993-06-09
• 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.
• Bisphosphonic acid derivatives as anti-arthritic agents
  申请人：The Upjohn Company

  公开号：US05412141A1

  公开（公告）日：1995-05-02

  The bisphosphonates of formula (III) R.sub.2 --X--(CW).sub.m1 --CR.sub.3 R.sub.4 --CH.sub.2 --CM[PO--(OR.sub.1).sub.2 ].sub.2 (III) 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.

  公式（III）中的双膦酸盐R.sub.2 --X--(CW).sub.m1 --CR.sub.3 R.sub.4 --CH.sub.2 --CM[PO--(OR.sub.1).sub.2 ].sub.2（III），双环双膦酸盐（V），和环状双膦酸盐（VII）可用作抗关节炎药物，并且不具有前列腺素合成酶抑制剂的副作用。
• 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.