U 81581 | 132508-03-3

• 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: U 81581
• 英文别名: <5-(cyclohexylcarbonyl)-2,4-dihydro-3H-pyrazol-3-ylidene>bisphosphonic acid tetraethyl ester；[5-(cyclohexylcarbonyl)-2,4-dihydro-3H-pyrazol-3-ylidene]bisphosphonic acid tetraethyl ester；[5,5-bis(diethoxyphosphoryl)-1,4-dihydropyrazol-3-yl]-cyclohexylmethanone
• CAS: 132508-03-3
• 化学式: C₁₈H₃₄N₂O₇P₂
• 分子量: 452.425
• InChiKey: PMNVVKUHKPNXNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  U 81581 在 三甲基溴硅烷 作用下， 以 氯仿 为溶剂， 反应 5.0h， 生成 <5-(cyclohexylcarbonyl)-2,4-dihydro-3H-pyrazol-3-ylidene>bisphosphonic acid dipotassium salt
  参考文献：
  名称：

  Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents

  摘要：

  Vinylidenebisphosphonic acid tetraethyl ester (1) and diazo ketones 7a-1 in ether at 22-degrees-C yield pyrazoline bisphosphonate tetraethyl esters 8a-1 in moderate to good yield. These compounds were evaluated in animal models of arthritis: rat adjuvant induced polyarthritis (AIP) and murine antigen-induced arthritis (AIA) and a murine model of chronic inflammation, the delayed type hypersensitivity granuloma reaction (DTH-GRA). (5-Benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)-bisphosphonic acid tetraethyl ester (8a), and [5-(3-fluorobenzoyl)-2,4-dihydro-3H-pyrazol-3-ylidene)bisphosphonic acid tetraethyl ester (8d) significantly inhibited the arthritis models, AIP (15 mg/kg) and AIA (25 mg/kg), as well as the DTH-GRA (25 mg/kg). Conversion of 8a to the corresponding bisphosphonic acid, 10a, resulted in loss of activity Compounds with alkyl substituents on the pyrazoline nitrogen, 9a-d, were inactive in the DTH-GRA. These results show that 8a and 8d have novel antiinflammatory activity and are capable of inhibiting chronic arthritis and inflammation in animals. Such compounds might be in man for treating chronic tissue injury associated with arthropathies such as inflammatory joint disease as well as other chronic inflammatory diseases.

  DOI：

  10.1021/jm00053a017
• 作为产物：
  描述：

  亚甲基二磷酸四乙酯 在 对甲苯磺酸 、 二乙胺 作用下， 以 乙醚 为溶剂， 反应 56.0h， 生成 U 81581
  参考文献：
  名称：

  Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents

  摘要：

  Vinylidenebisphosphonic acid tetraethyl ester (1) and diazo ketones 7a-1 in ether at 22-degrees-C yield pyrazoline bisphosphonate tetraethyl esters 8a-1 in moderate to good yield. These compounds were evaluated in animal models of arthritis: rat adjuvant induced polyarthritis (AIP) and murine antigen-induced arthritis (AIA) and a murine model of chronic inflammation, the delayed type hypersensitivity granuloma reaction (DTH-GRA). (5-Benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)-bisphosphonic acid tetraethyl ester (8a), and [5-(3-fluorobenzoyl)-2,4-dihydro-3H-pyrazol-3-ylidene)bisphosphonic acid tetraethyl ester (8d) significantly inhibited the arthritis models, AIP (15 mg/kg) and AIA (25 mg/kg), as well as the DTH-GRA (25 mg/kg). Conversion of 8a to the corresponding bisphosphonic acid, 10a, resulted in loss of activity Compounds with alkyl substituents on the pyrazoline nitrogen, 9a-d, were inactive in the DTH-GRA. These results show that 8a and 8d have novel antiinflammatory activity and are capable of inhibiting chronic arthritis and inflammation in animals. Such compounds might be in man for treating chronic tissue injury associated with arthropathies such as inflammatory joint disease as well as other chronic inflammatory diseases.

  DOI：

  10.1021/jm00053a017

文献信息

• Geminal bisphosphonic acids and derivatives as anti-arthritic agents
  申请人：The Upjohn Company

  公开号：US05220021A1

  公开（公告）日：1993-06-15

  Unsaturated geminal phosphonates (III) ##STR1## either as the esters, free acids or salts are useful in the treatment of arthritis.

  不饱和的磷酰亚磷酸(III)无论是作为酯、游离酸还是盐，在治疗关节炎方面都有用。
• GEMINAL BISPHOSPHONIC ACIDS AND DERIVATIVES AS ANTI-ARTHRITIC AGENTS
  申请人：THE UPJOHN COMPANY

  公开号：EP0466730A1

  公开（公告）日：1992-01-22
• US5220021A
  申请人：——

  公开号：US5220021A

  公开（公告）日：1993-06-15
• [EN] GEMINAL BISPHOSPHONIC ACIDS AND DERIVATIVES AS ANTI-ARTHRITIC AGENTS
  申请人：THE UPJOHN COMPANY

  公开号：WO1990012017A1

  公开（公告）日：1990-10-18

  (EN) Unsaturated geminal phosphonates (III), either as the esters, free acids or salts are useful in the treatment of arthritis.(FR) L'invention concerne des phosponates germinaux insaturés (III) à titre soit d'esters, d'acides ou de sels libres utiles dans le traitement de l'arthrite.
• Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents
  作者：Richard A. Nugent、Megan Murphy、Stephen T. Schlachter、Colin J. Dunn、Robert J. Smith、Nigel D. Staite、Louise A. Galinet、Sharon K. Shields、Danielle G. Aspar、Karen A. Richard、Norman A. Rohloff

  DOI：10.1021/jm00053a017

  日期：1993.1

  Vinylidenebisphosphonic acid tetraethyl ester (1) and diazo ketones 7a-1 in ether at 22-degrees-C yield pyrazoline bisphosphonate tetraethyl esters 8a-1 in moderate to good yield. These compounds were evaluated in animal models of arthritis: rat adjuvant induced polyarthritis (AIP) and murine antigen-induced arthritis (AIA) and a murine model of chronic inflammation, the delayed type hypersensitivity granuloma reaction (DTH-GRA). (5-Benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)-bisphosphonic acid tetraethyl ester (8a), and [5-(3-fluorobenzoyl)-2,4-dihydro-3H-pyrazol-3-ylidene)bisphosphonic acid tetraethyl ester (8d) significantly inhibited the arthritis models, AIP (15 mg/kg) and AIA (25 mg/kg), as well as the DTH-GRA (25 mg/kg). Conversion of 8a to the corresponding bisphosphonic acid, 10a, resulted in loss of activity Compounds with alkyl substituents on the pyrazoline nitrogen, 9a-d, were inactive in the DTH-GRA. These results show that 8a and 8d have novel antiinflammatory activity and are capable of inhibiting chronic arthritis and inflammation in animals. Such compounds might be in man for treating chronic tissue injury associated with arthropathies such as inflammatory joint disease as well as other chronic inflammatory diseases.