2,3-dihydro-5-(2-chloropyridin-4-yl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine | 123412-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯嗪
• 英文名称: 2,3-dihydro-5-(2-chloropyridin-4-yl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine
• 英文别名: [3-(2-chloropyridin-4-yl)-2-(hydroxymethyl)-6,7-dihydro-5H-pyrrolizin-1-yl]methanol
• CAS: 123412-55-5
• 化学式: C₁₄H₁₅ClN₂O₂
• 分子量: 278.738
• InChiKey: DEMGSZXORJIAAW-UHFFFAOYSA-N

物化性质

• 熔点：
  145-149 °C
• 沸点：
  505.9±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.28
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-5-(2-chloropyridin-4-yl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine 、 异氰酸异丙酯 在 dibutyltin diacetate 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以41%的产率得到2,3-dihydro-5-(2-chloropyridin-4-yl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(N-2-propylcarbamate)
  参考文献：
  名称：

  Vinylogous carbinolamine tumor inhibitors. 24. Synthesis, chemistry, and antineoplastic activity of .alpha.-halopyridinium salts: potential pyridone prodrugs of acylated vinylogous carbinolamine tumor inhibitors.

  摘要：

  A series of 4- and 5-[2,3-dihydro-6,7-bis[[(N-alkylcarbamoyl)oxy]methyl]-1H-pyrrol izin-5- yl]-2-halopyridinium iodides were synthesized. The rates of hydrolysis of the alpha-halopyridinium salts to the corresponding pyridones, and the reactivities of the carbamate moieties were studied as a function of pH, buffer composition, and ionic strength. The 4- and 5-pyrrolizinyl-2-halopyridinium iodides and the corresponding pyridones were evaluated against P388 lymphocytic leukemia in vivo. The alpha-fluoropyridinium compounds were active but the alpha-chloro compounds were not. This activity was correlated with the rates of hydrolysis of the alpha-halopyridinium compounds to the active pyridone. Compounds that were active in the P388 screen were evaluated in L1210 leukemia, M5076 carcinoma, and MX-1 mammary xenograft assays in mice.

  DOI：

  10.1021/jm00168a021
• 作为产物：
  描述：

  dimethyl 2,3-dihydro-5-(2-chloropyridin-4-yl)-1H-pyrrolizine-6,7-dicarboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以91%的产率得到2,3-dihydro-5-(2-chloropyridin-4-yl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine
  参考文献：
  名称：

  Vinylogous carbinolamine tumor inhibitors. 24. Synthesis, chemistry, and antineoplastic activity of .alpha.-halopyridinium salts: potential pyridone prodrugs of acylated vinylogous carbinolamine tumor inhibitors.

  摘要：

  A series of 4- and 5-[2,3-dihydro-6,7-bis[[(N-alkylcarbamoyl)oxy]methyl]-1H-pyrrol izin-5- yl]-2-halopyridinium iodides were synthesized. The rates of hydrolysis of the alpha-halopyridinium salts to the corresponding pyridones, and the reactivities of the carbamate moieties were studied as a function of pH, buffer composition, and ionic strength. The 4- and 5-pyrrolizinyl-2-halopyridinium iodides and the corresponding pyridones were evaluated against P388 lymphocytic leukemia in vivo. The alpha-fluoropyridinium compounds were active but the alpha-chloro compounds were not. This activity was correlated with the rates of hydrolysis of the alpha-halopyridinium compounds to the active pyridone. Compounds that were active in the P388 screen were evaluated in L1210 leukemia, M5076 carcinoma, and MX-1 mammary xenograft assays in mice.

  DOI：

  10.1021/jm00168a021

文献信息

• ANDERSON, WAYNE K.;DEAN, DENNIS C.;ENDO, TOSHIYASU, J. MED. CHEM., 33,(1990) N, C. 1667-1675
  作者：ANDERSON, WAYNE K.、DEAN, DENNIS C.、ENDO, TOSHIYASU

  DOI：——

  日期：——