(5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)biphosphonic acid tetraethyl ester | 132508-02-2

• 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: (5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)biphosphonic acid tetraethyl ester
• 英文别名: [5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene]bisphosphonic acid tetraethyl ester；5-benzoyl-3,4-dihydro-2H-pyrazole-3,3-diphosphonic acid tetraethyl ester；U-81581；Tetraethyl (5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)bisphosphonate；[5,5-bis(diethoxyphosphoryl)-1,4-dihydropyrazol-3-yl]-phenylmethanone
• CAS: 132508-02-2
• 化学式: C₁₈H₂₈N₂O₇P₂
• 分子量: 446.377
• InChiKey: NPLHDPAQRZJWHX-UHFFFAOYSA-N

物化性质

• 沸点：
  564.6±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  (5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)biphosphonic acid tetraethyl ester 在 三甲基溴硅烷 作用下， 以 氯仿 为溶剂， 反应 5.0h， 生成 (5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)bisphosphonic acid disodium 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 (5-benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)biphosphonic acid tetraethyl ester
  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。
• [EN] QUINOLINES AS INHIBITORS OF FARNESYL PYROPHOSPHATE SYNTHASE<br/>[FR] QUINOLÉINES EN TANT QU'INHIBITEURS DE LA FARNÉSYL PYROPHOSPHATE SYNTHASE
  申请人：NOVARTIS AG

  公开号：WO2009106586A1

  公开（公告）日：2009-09-03

  The invention relates to a compound of formula (I) wherein the substituents are as described in the specification, which are useful as farnesyl pyrophosphate synthase modulators, e.g. in the treatment of proliferative diseases, to methods of manufacturing such compounds and to intermediates thereof.

  本发明涉及式(I)化合物，其中取代基如说明书中所述，这些化合物作为法尼基焦磷酸合酶调节剂是有用的，例如在增殖性疾病的治疗中，涉及制造这些化合物的方法及其中间体。
• Method of administering bisphosphonates
  申请人：——

  公开号：US20030181421A1

  公开（公告）日：2003-09-25

  Bisphosphonates, in particular more potent N-bisphosphonates such as zoledronic acid and derivatives, can be used with satisfactory results for prolonged inhibition of bone resorption in conditions of abnormally increased bone turnover, e.g. osteoporosis, by intermittent administration, wherein the periods between bisphosphonate administrations are longer than was previously considered appropriate, e.g. a dosing interval of at least about 6 months or less frequently.

  双膦酸盐，特别是更强效的N-双膦酸盐，如左氧磷酸和衍生物，可以通过间歇性给药获得令人满意的结果，长期抑制骨质疏松等异常增加骨转换的情况中的骨吸收，例如骨质疏松症，其中双膦酸盐给药之间的间隔时间比以前认为适当的更长，例如至少大约6个月或更少频繁的给药间隔。
• Use of bisphosphonates for pain treatment
  申请人：——

  公开号：US20040063670A1

  公开（公告）日：2004-04-01

  A method for the treatment of pain, in particular antinociceptive or anti-allodynic treatment of pain, in a patient in need of such treatment, e.g. a patient with osteoporosis or osteopenia, a tumour patient or a patient suffering from an inflammatory disease, which comprises administering an effective amount of a bisphosphonate, e.g. zoledronic acid or salts or hydrates thereof, to the patient.

  一种用于治疗疼痛的方法，特别是用于需要这种治疗的患者，例如骨质疏松症或骨质疏松症患者、肿瘤患者或患有炎症性疾病的患者的镇痛或抗痛觉过敏治疗，包括向患者施用有效量的双膦酸盐，例如唑来膦酸或其盐或水合物。
• [EN] SALICYLIC ACID DERIVATIVES BEING FARNESYL PYROPHOSPHATE SYNTHASE ACTIVITY INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE SALICYLIQUE EN TANT QU'INHIBITEURS DE L'ACTIVITÉ FARNÉSYLPYROPHOSPHATE SYNTHASE
  申请人：NOVARTIS AG

  公开号：WO2010043584A1

  公开（公告）日：2010-04-22

  The invention relates to the use of and mainly novel compounds of the formula (I) wherein the moieties are as defined in the description, which are useful as farnesyl pyrophosphate synthase modulators and e.g. in the treatment of proliferative diseases.

  该发明涉及使用主要是新颖化合物的公式（I），其中基团如描述中定义的，这些化合物可用作法尼基焦磷酸合酶调节剂，例如用于治疗增殖性疾病。