(2,5-Dioxopyrrolidin-1-yl) 3,3-bis(diethoxyphosphoryl)propanoate | 1036739-08-8

• 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: (2,5-Dioxopyrrolidin-1-yl) 3,3-bis(diethoxyphosphoryl)propanoate
• CAS: 1036739-08-8
• 化学式: C₁₅H₂₇NO₁₀P₂
• 分子量: 443.328
• InChiKey: WNQDIRJOUIGSPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2,5-Dioxopyrrolidin-1-yl) 3,3-bis(diethoxyphosphoryl)propanoate 、 奥利万星 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以12%的产率得到
  参考文献：
  名称：

  Synthesis and in vitro evaluation of bisphosphonated glycopeptide prodrugs for the treatment of osteomyelitis

  摘要：

  As therapeutic agents of choice in the treatment of complicated infections, glycopeptide antibiotics are often preferentially used in cases of osteomyelitis, an infection located in bone and notoriously difficult to successfully manage. Yet frequent and heavy doses of these systemically administered antibiotics are conventionally prescribed to obtain higher antibiotic levels in the bone and reduce the high recurrence rates. Targeting antibiotics to the bone after systemic administration would present at least three potential advantages: (i) greater efficacy, by concentrating the therapeutic agent in bone; (ii) greater convenience, through a reduction in the frequency of administration; and (iii) greater safety, by reducing the levels of systemic drug exposure. We present here the design, synthesis and in vitro evaluation of eight prodrugs of the glycopeptide antibacterial agents vancomycin and oritavancin taking advantage of the affinity of the bisphosphonate group for bone for delivery to osseous tissues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.006
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 3,3-二(二乙氧基磷酰)丙酸 在 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 以100%的产率得到(2,5-Dioxopyrrolidin-1-yl) 3,3-bis(diethoxyphosphoryl)propanoate
  参考文献：
  名称：

  Synthesis and in vitro evaluation of bisphosphonated glycopeptide prodrugs for the treatment of osteomyelitis

  摘要：

  As therapeutic agents of choice in the treatment of complicated infections, glycopeptide antibiotics are often preferentially used in cases of osteomyelitis, an infection located in bone and notoriously difficult to successfully manage. Yet frequent and heavy doses of these systemically administered antibiotics are conventionally prescribed to obtain higher antibiotic levels in the bone and reduce the high recurrence rates. Targeting antibiotics to the bone after systemic administration would present at least three potential advantages: (i) greater efficacy, by concentrating the therapeutic agent in bone; (ii) greater convenience, through a reduction in the frequency of administration; and (iii) greater safety, by reducing the levels of systemic drug exposure. We present here the design, synthesis and in vitro evaluation of eight prodrugs of the glycopeptide antibacterial agents vancomycin and oritavancin taking advantage of the affinity of the bisphosphonate group for bone for delivery to osseous tissues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.006

文献信息

• PHOSPHONATED GLYCOPEPTIDE AND LIPOGLYCOPEPTIDE ANTIBIOTICS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
  申请人：Tanaka Kelly

  公开号：US20100113333A1

  公开（公告）日：2010-05-06

  The present invention is directed to antimicrobial compounds which have an affinity for binding bones. More particularly, the invention is directed to phosphonated derivatives of glycopeptide or lipoglycopeptide antibiotics. These compounds are useful as antibiotics for the prevention or treatment of bone and joint infections, especially for the prevention and treatment of osteomyelitis.

  本发明涉及具有与骨骼结合亲和力的抗微生物化合物。更具体地，该发明涉及磷酸酯化的糖肽类或脂质糖肽类抗生素的衍生物。这些化合物可用作抗生素，用于预防或治疗骨骼和关节感染，特别是用于预防和治疗骨髓炎。
• US8946144B2
  申请人：——

  公开号：US8946144B2

  公开（公告）日：2015-02-03
• [EN] PHOSPHONATED GLYCOPEPTIDE AND LIPOGLYCOPEPTIDE ANTIBIOTICS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS<br/>[FR] ANTIBIOTIQUES À BASE DE GLYCOPEPTIDES ET DE LIPOGLYCOPEPTIDES PHOSPHONÉS ET LEURS UTILISATIONS DANS LA PRÉVENTION ET LE TRAITEMENT D'INFECTIONS OSSEUSES ET ARTICULAIRES
  申请人：TARGANTA THERAPEUTICS INC

  公开号：WO2008077241A1

  公开（公告）日：2008-07-03

  [EN] The present invention is directed to antimicrobial compounds which have an affinity for binding bones. More particularly, the invention is directed to phosphonated derivatives of glycopeptide or lipoglycopeptide antibiotics. These compounds are useful as antibiotics for the prevention or treatment of bone and joint infections, especially for the prevention and treatment of osteomyelitis.
  [FR] La présente invention concerne des composés antimicrobiens qui présentent une affinité pour se lier aux os. Plus particulièrement, l'invention concerne des dérivés phosphonés d'antibiotiques à base de glycopeptides ou de lipopeptides. Ces composés sont utiles comme antibiotiques pour la prévention ou le traitement d'infections osseuses et articulaires, en particulier pour la prévention et le traitement de l'ostéomyélite.
• Synthesis and in vitro evaluation of bisphosphonated glycopeptide prodrugs for the treatment of osteomyelitis
  作者：Kelly S.E. Tanaka、Evelyne Dietrich、Stéphane Ciblat、Claude Métayer、Francis F. Arhin、Ingrid Sarmiento、Gregory Moeck、Thomas R. Parr、Adel Rafai Far

  DOI：10.1016/j.bmcl.2010.01.006

  日期：2010.2

  As therapeutic agents of choice in the treatment of complicated infections, glycopeptide antibiotics are often preferentially used in cases of osteomyelitis, an infection located in bone and notoriously difficult to successfully manage. Yet frequent and heavy doses of these systemically administered antibiotics are conventionally prescribed to obtain higher antibiotic levels in the bone and reduce the high recurrence rates. Targeting antibiotics to the bone after systemic administration would present at least three potential advantages: (i) greater efficacy, by concentrating the therapeutic agent in bone; (ii) greater convenience, through a reduction in the frequency of administration; and (iii) greater safety, by reducing the levels of systemic drug exposure. We present here the design, synthesis and in vitro evaluation of eight prodrugs of the glycopeptide antibacterial agents vancomycin and oritavancin taking advantage of the affinity of the bisphosphonate group for bone for delivery to osseous tissues. (C) 2010 Elsevier Ltd. All rights reserved.