diethyl 3-(m-trimethylsilylphenyl)propyl-1-phosphonate | 410092-66-9

• 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: diethyl 3-(m-trimethylsilylphenyl)propyl-1-phosphonate
• 英文别名: [3-(3-Diethoxyphosphorylpropyl)phenyl]-trimethylsilane
• CAS: 410092-66-9
• 化学式: C₁₆H₂₉O₃PSi
• 分子量: 328.464
• InChiKey: SQIWVKLWSLCCLC-UHFFFAOYSA-N

物化性质

• 沸点：
  403.0±28.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  diethyl 3-(m-trimethylsilylphenyl)propyl-1-phosphonate 在 乙醇 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 3-(m-trimethylsilylphenyl)propylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  Studies on the Synthesis and Biological Properties of Non-Carrier-Added [¹²⁵I and ¹³¹I]-Labeled Arylalkylidenebisphosphonates:  Potent Bone-Seekers for Diagnosis and Therapy of Malignant Osseous Lesions

  摘要：

  Arylalkylidenebisphosphonates labeled with nca [I-125 or I-131] have been synthesized and their biological function investigated. The label was attached to the aromatic group in high yield and under mild conditions by means of iododesilylation. The bone affinities of the radioactive compounds were investigated in normal Balb/C mice. The compound 1-hydroxy(m-iodo[I-125,I-131]- phenylethylidene)-1,1-bisphosphonate was found to possess superior bone affinity compared to others, and its in vivo deiodination was insignificant. The uptake in femur 24h after injection was 850 +/- 265% and 986 +/- 118% of injected dose per gram tissue times gram body weight in mice and rats, respectively. The therapeutic potential of the compound was investigated in two tumor models in athymic (nude) rats, one model for mixed lytic/sclerotic metastatic bonelesions originating from breast cancer and the other model simulating osseous osteosarcoma. The effects in these models compare favorably to those observed for established treatment modalities. The experiments demonstrate that radioiodinated bisphosphonates may have a potential for diagnosis and therapy of malignant osseous lesions.

  DOI：

  10.1021/jm021107v
• 作为产物：
  描述：

  [3-(溴甲基)苯基]-三甲基硅烷 在 Oxone 、 sodium hydroxide 、 disodium hydrogenphosphate 、 sodium amalgam 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 5.67h， 生成 diethyl 3-(m-trimethylsilylphenyl)propyl-1-phosphonate
  参考文献：
  名称：

  Studies on the Synthesis and Biological Properties of Non-Carrier-Added [¹²⁵I and ¹³¹I]-Labeled Arylalkylidenebisphosphonates:  Potent Bone-Seekers for Diagnosis and Therapy of Malignant Osseous Lesions

  摘要：

  Arylalkylidenebisphosphonates labeled with nca [I-125 or I-131] have been synthesized and their biological function investigated. The label was attached to the aromatic group in high yield and under mild conditions by means of iododesilylation. The bone affinities of the radioactive compounds were investigated in normal Balb/C mice. The compound 1-hydroxy(m-iodo[I-125,I-131]- phenylethylidene)-1,1-bisphosphonate was found to possess superior bone affinity compared to others, and its in vivo deiodination was insignificant. The uptake in femur 24h after injection was 850 +/- 265% and 986 +/- 118% of injected dose per gram tissue times gram body weight in mice and rats, respectively. The therapeutic potential of the compound was investigated in two tumor models in athymic (nude) rats, one model for mixed lytic/sclerotic metastatic bonelesions originating from breast cancer and the other model simulating osseous osteosarcoma. The effects in these models compare favorably to those observed for established treatment modalities. The experiments demonstrate that radioiodinated bisphosphonates may have a potential for diagnosis and therapy of malignant osseous lesions.

  DOI：

  10.1021/jm021107v

文献信息

• Bis-phosphonate compounds
  申请人：——

  公开号：US06548042B2

  公开（公告）日：2003-04-15

  The present invention provides a pharmaceutical compound, or pharmaceutically acceptable salt thereof, for use in medicine, wherein said compound is of formula I wherein R is a pharmaceutically active moiety; Ar is an aromatic moiety; X is a linker group; and Y is a moiety comprising two phosphonate groups. Further aspects of the invention relate to a method for palliative and curative treatment of bone disorders and cancer related disorders, such as breast cancer.

  本发明提供了一种药物化合物，或其药用可接受的盐，用于医学上的使用，其中所述化合物为式I，其中R为药用活性基团；Ar为芳香基团；X为连接基团；Y为包含两个膦酸酯基团的基团。该发明的进一步方面涉及一种用于对骨骼疾病和癌症相关疾病（如乳腺癌）进行姑息治疗和治疗的方法。
• Studies on the Synthesis and Biological Properties of Non-Carrier-Added [¹²⁵I and ¹³¹I]-Labeled Arylalkylidenebisphosphonates:  Potent Bone-Seekers for Diagnosis and Therapy of Malignant Osseous Lesions
  作者：Erik Årstad、Per Hoff、Lars Skattebøl、Arne Skretting、Knut Breistøl

  DOI：10.1021/jm021107v

  日期：2003.7.1

  Arylalkylidenebisphosphonates labeled with nca [I-125 or I-131] have been synthesized and their biological function investigated. The label was attached to the aromatic group in high yield and under mild conditions by means of iododesilylation. The bone affinities of the radioactive compounds were investigated in normal Balb/C mice. The compound 1-hydroxy(m-iodo[I-125,I-131]- phenylethylidene)-1,1-bisphosphonate was found to possess superior bone affinity compared to others, and its in vivo deiodination was insignificant. The uptake in femur 24h after injection was 850 +/- 265% and 986 +/- 118% of injected dose per gram tissue times gram body weight in mice and rats, respectively. The therapeutic potential of the compound was investigated in two tumor models in athymic (nude) rats, one model for mixed lytic/sclerotic metastatic bonelesions originating from breast cancer and the other model simulating osseous osteosarcoma. The effects in these models compare favorably to those observed for established treatment modalities. The experiments demonstrate that radioiodinated bisphosphonates may have a potential for diagnosis and therapy of malignant osseous lesions.