2,3-dihydro-5-(4-pyridinyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(N-2-propylcarbamate) | 123412-56-6

• 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-(4-pyridinyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(N-2-propylcarbamate)
• 英文别名: 2,3-dihydro-5-(4-pyridinyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine Bis[N-(2-propyl)carbamate]；[2-(propan-2-ylcarbamoyloxymethyl)-3-pyridin-4-yl-6,7-dihydro-5H-pyrrolizin-1-yl]methyl N-propan-2-ylcarbamate
• CAS: 123412-56-6
• 化学式: C₂₂H₃₀N₄O₄
• 分子量: 414.505
• InChiKey: WUXKAYDOFLHBGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  94.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-5-(4-pyridinyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(N-2-propylcarbamate) 、 碘甲烷 生成 1-methyl-4-<2,3-dihydro-6,7-bis<<(N-2-propylcarbamoyl)oxy>methyl>-1H-pyrrolizin-5-yl>pyridinium iodide
  参考文献：
  名称：

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

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氟异烟酸 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 氯化亚砜 、 dibutyltin diacetate 、 氢气 、 乙酸酐 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， -15.0~75.0 ℃ 、241.32 kPa 条件下， 反应 77.0h， 生成 2,3-dihydro-5-(4-pyridinyl)-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

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：——
• BIS-ACYLOXYMETHYL DERIVATIVES
  申请人：THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK

  公开号：EP0479951A1

  公开（公告）日：1992-04-15
• US5583148A
  申请人：——

  公开号：US5583148A

  公开（公告）日：1996-12-10
• [EN] BIS-ACYLOXYMETHYL DERIVATIVES
  申请人：THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK

  公开号：WO1991000093A1

  公开（公告）日：1991-01-10

  (EN) This invention relates to new pyridyl, quinoline and acridine bis-acyloxymethyl compounds; to compositions comprising these compounds; and to processes for their utility as fungicides, bactericides and as inhibitors of the growth of cancer in warm-blooded animals. In accordance with this invention, new bis-acyloxymethyl derivatives are provided of formula (I), wherein A is hydrogen, or, A and B are independently selected from substituted and unsubstituted alkyl, cycloalkyl, aryl, alkenyl, cycloalkenyl and alkynyl, or, A and B together comprise a pyrrolizine; L is selected from (II); (III); (IV); and, (V), wherein Y is selected from hydrogen or (VI); each R and Z is independently selected from hydrogen or substituted and unsubstituted alkyl, cycloalkyl, aryl, alkenyl, cycloalkenyl, alkynyl, amine, carboxylic acid group, carboxylic acid ester group, carboxylic acid amide group, sulfonic acid group and sulfonic acid amide group; each Z' is independently selected from hydrogen and substituted or unsubstituted alkyl; M is Z or is selected from halogen, nitro, hydroxyl and substituted or unsubstituted, nitrile, ether, thioether, acylated hydroxyl, sulfonylamide, sulfonylurea, sulfoxide, sulfone and mixtures thereof; each n is the same and is 0 or 1; q is from 0 to 4; and, X is the anion of an acid.(FR) L'invention concerne des nouveaux composés de bis-acyloxyméthyle pyridyle, quinoline et acridine; des compositions comprenant ces composés, ainsi que des procédés les mettant en ÷uvre en tant que fongicides bactéricides et inhibiteurs de la croissance du cancer chez les animaux à sang chaud. Selon l'invention, les nouveaux dérivés de bis-acyloxyméthyle ont la formule (I), dans laquelle A représente hydrogène, ou A et B sont indépendamment choisis entre alkyle, cycloalkyle, aryle, alcényle, cycloalcényle et alkynyle substitués et non substitués, ou A et B comprennent ensemble une pyrrolizine; L est choisi entre (II); (III); (IV); et, (V), dans lesquels Y est choisi entre hydrogène ou (VI); chaque R et Z est choisi indépendamment entre hydrogène ou alkyle, cycloalkyle, aryle, alcényle, cycloalcényle, alkynyle, amine, un groupe d'acide carboxylique, un groupe d'esters d'acide carboxylique, un groupe d'amides d'acide carboxylique, un groupe d'acides sulfoniques et un groupe d'amides d'acides sulfoniques substitués et non substitués; chaque Z' est choisi indépendamment entre hydrogène et alkyle substitués ou non substitués; M représente Z ou est choisi entre halogène, nitro, hydroxyle et nitrile, éther, thioéther, hydroxyle acylé, sulfonylamide, sulfonylurée, sulfoxyde, sulfone substitués ou non substitués ainsi que des mélanges de ces derniers; chaque n est identique et représente 0 ou 1; q est compris entre 0 et 4; X représente l'anion d'un acide.
• Vinylogous carbinolamine tumor inhibitors. 24. Synthesis, chemistry, and antineoplastic activity of .alpha.-halopyridinium salts: potential pyridone prodrugs of acylated vinylogous carbinolamine tumor inhibitors.
  作者：Wayne K. Anderson、Dennis C. Dean、Toshiyasu Endo

  DOI：10.1021/jm00168a021

  日期：1990.6

  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.