3-(N,N-bis(2-chloroethyl)carbamoyl)pyridine | 99360-31-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(N,N-bis(2-chloroethyl)carbamoyl)pyridine
• 英文别名: nicotinic acid-[bis-(2-chloro-ethyl)-amide]；Nicotinsaeure-[bis-(2-chlor-aethyl)-amid]；N,N-bis(2-chloroethyl)pyridine-3-carboxamide
• CAS: 99360-31-3
• 化学式: C₁₀H₁₂Cl₂N₂O
• 分子量: 247.124
• InChiKey: FINQDBRANXXAGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(N,N-bis(2-chloroethyl)carbamoyl)pyridine 在 sodium dithionite 、 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 27.0h， 生成 1-propyl-3-{bis(2-chloroethyl)carbamoyl}-1,4-dihydropyridine
  参考文献：
  名称：

  Synthesis in vitro/in vivo evaluation and in silico physicochemical study of prodrug approach for brain targeting of alkylating agent

  摘要：

  Every year, there are more than two lakhs of population affected with CNS tumor. Nitrogen mustard class of alkylating drugs, used clinically against various types of tumor, is too polar to cross the BBB. The redox chemical drug delivery prodrug approach is one of the most interesting procedures for delivering drugs in a sustained and specific manner to the CNS. The objective of the present study is to investigate the redox drug delivery system for the delivery of bis(2-chloroethyl)amine (nor mustard) as alkylating cytotoxic agent to the brain. Various redox derivatives of CDS-M (4a-d) were synthesized incorporating different alkyl/aryl moieties at ring nitrogen and subjected to in silico physicochemical parameters determination required for CNS activity through computational, online, and QikProp 3.2 software. The results of stability study, in vitro chemical (silver nitrate), and biological oxidation studies in human blood, rat blood, and brain homogenate for all CDS-M (4a-d) have been promising and suggest that brain targeting could be possible with more stable CDS-M (4d). The in vivo study showed that CDS-M (4d) was able to cross the BBB at detectable concentrations, and in vitro NBP alkylating activity of its quaternary salt (3d) was comparable to the known drug chlorambucil among all the synthesized derivatives.

  DOI：

  10.1007/s00044-013-0537-0
• 作为产物：
  描述：

  烟酸 、 二(2-氯乙基)氯化铵 在 氯化亚砜 、 氯仿 、 苯 作用下， 生成 3-(N,N-bis(2-chloroethyl)carbamoyl)pyridine
  参考文献：
  名称：

  Michailow; Kosminskaja, Zhurnal Obshchei Khimii, 1956, vol. 26, p. 2042,2045; engl. Ausg. S. 2275

  摘要：

  DOI：

文献信息

• Drefahl; Koenig, Chemische Berichte, 1954, vol. 87, p. 1632
  作者：Drefahl、Koenig

  DOI：——

  日期：——
• Michailow; Kosminskaja, Zhurnal Obshchei Khimii, 1956, vol. 26, p. 2042,2045; engl. Ausg. S. 2275
  作者：Michailow、Kosminskaja

  DOI：——

  日期：——
• Synthesis in vitro/in vivo evaluation and in silico physicochemical study of prodrug approach for brain targeting of alkylating agent
  作者：Rajesh K. Singh、D. N. Prasad、T. R. Bhardwaj

  DOI：10.1007/s00044-013-0537-0

  日期：2013.11

  Every year, there are more than two lakhs of population affected with CNS tumor. Nitrogen mustard class of alkylating drugs, used clinically against various types of tumor, is too polar to cross the BBB. The redox chemical drug delivery prodrug approach is one of the most interesting procedures for delivering drugs in a sustained and specific manner to the CNS. The objective of the present study is to investigate the redox drug delivery system for the delivery of bis(2-chloroethyl)amine (nor mustard) as alkylating cytotoxic agent to the brain. Various redox derivatives of CDS-M (4a-d) were synthesized incorporating different alkyl/aryl moieties at ring nitrogen and subjected to in silico physicochemical parameters determination required for CNS activity through computational, online, and QikProp 3.2 software. The results of stability study, in vitro chemical (silver nitrate), and biological oxidation studies in human blood, rat blood, and brain homogenate for all CDS-M (4a-d) have been promising and suggest that brain targeting could be possible with more stable CDS-M (4d). The in vivo study showed that CDS-M (4d) was able to cross the BBB at detectable concentrations, and in vitro NBP alkylating activity of its quaternary salt (3d) was comparable to the known drug chlorambucil among all the synthesized derivatives.