[3-(3,4-二氯苯基)-2-(丙-2-基氨基甲酰氧基甲基)-6,7-二氢-5H-吡咯里嗪-1-基]甲基N-丙-2-基氨基甲酸酯 | 74296-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: [3-(3,4-二氯苯基)-2-(丙-2-基氨基甲酰氧基甲基)-6,7-二氢-5H-吡咯里嗪-1-基]甲基N-丙-2-基氨基甲酸酯
• 英文名称: NSC 278214
• 英文别名: 5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-2,3-dihydro-1H-pyrrolizine bis(2-propylcarbamate)；Carbamic acid, (1-methylethyl)-, (5-(3,4-dichlorophenyl)-2,3-dihydro-1H-pyrrolizine-6,7-diyl)bis(methylene) ester；[3-(3,4-dichlorophenyl)-2-(propan-2-ylcarbamoyloxymethyl)-6,7-dihydro-5H-pyrrolizin-1-yl]methyl N-propan-2-ylcarbamate
• CAS: 74296-42-7
• 化学式: C₂₃H₂₉Cl₂N₃O₄
• 分子量: 482.407
• InChiKey: CCBHSPUYWZHDFX-UHFFFAOYSA-N

物化性质

• 沸点：
  640.6±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  81.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [3-(3,4-二氯苯基)-2-(丙-2-基氨基甲酰氧基甲基)-6,7-二氢-5H-吡咯里嗪-1-基]甲基N-丙-2-基氨基甲酸酯 在 水 作用下， 以 乙腈 为溶剂， 生成 Isopropyl-carbamic acid 3-(3,4-dichloro-phenyl)-1-hydroxymethyl-6,7-dihydro-5H-pyrrolizin-2-ylmethyl ester
  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：

  2,3-dihydro-5-(3',4'-dichlorophenyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine 、 异氰酸异丙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以81%的产率得到[3-(3,4-二氯苯基)-2-(丙-2-基氨基甲酰氧基甲基)-6,7-二氢-5H-吡咯里嗪-1-基]甲基N-丙-2-基氨基甲酸酯
  参考文献：
  名称：

  Anderson; New; Corey, Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 5, p. 765 - 767

  摘要：

  DOI：

文献信息

• SYNTHESIS OF 4H-BENZO[D]PYRROLO[1,2-A]THIAZOLES AND INDOLIZINO[6,7-b]INDOLE DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS
  申请人：Su Tsann-Long

  公开号：US20130178629A1

  公开（公告）日：2013-07-11

  The present invention provides a series of 2,3-bis(hydroxymethyl)-4H-benzo[d]pyrrolo-[1,2-a]thiazoles and 1,2-bis(hydroxymethyl)indolizino[6,7-b]indole derivatives and their bis(alkylcarbamates) derivatives. These derivatives were designed as bi-functional DNA cross-linking agents. The in vitro cytotoxicity study of these compounds revealed that they exhibit significant anti-proliferative activity in inhibiting human lymphoblastic leukemia and various solid tumor cell growth. The compounds also exhibit therapeutic efficacy against human breast carcinoma and lung cancer in xenograft model. The compounds generally possess potent antitumor activity to kill various human solid tumors and have high potential for clinical applications.

  本发明提供了一系列2,3-双(羟甲基)-4H-苯并[d]吡咯-[1,2-a]噻唑和1,2-双(羟甲基)吲哚并[6,7-b]吲哚衍生物及其双(烷基氨基甲酸酯)衍生物。这些衍生物被设计为具有双功能DNA交联作用的剂。对这些化合物进行的体外细胞毒性研究表明，它们在抑制人淋巴母细胞白血病和各种实体肿瘤细胞生长方面表现出显著的抗增殖活性。这些化合物还在异种移植模型中对人类乳腺癌和肺癌表现出治疗效果。这些化合物通常具有强大的抗肿瘤活性，可以杀死各种人类实体肿瘤，并具有高潜力用于临床应用。
• US4734423A
  申请人：——

  公开号：US4734423A

  公开（公告）日：1988-03-29
• US8703951B2
  申请人：——

  公开号：US8703951B2

  公开（公告）日：2014-04-22
• [EN] NOVEL PYRROLIZINE DERIVATIVES, THEIR SALTS OR SOLVATES HAVING ANTI-TUMOR ACTIVITY, AND PROCESSES FOR PREPARING THEM<br/>[FR] NOUVEAUX DERIVES DE PYRROLIZINE, LEURS SELS OU SOLVATES A ACTIVITE ANTITUMORALE, ET PROCEDES DE PREPARATION DE CES DERIVES
  申请人：GENECHEM INC.

  公开号：WO1998027095A1

  公开（公告）日：1998-06-25

  (EN) The present invention relates to novel pyrrolizine derivatives of formula (1), their salts or their solvates, and relates to the use of the compounds as anti-tumor medicines or as site-specific DNA alkylating agents in the gene relating technologies, the compounds and their salts which are so soluble into water-soluble solvents and stable in bodies as to be capable of being used as anti-tumor medicines and in addition to this, can be so bound with the materials site-specifically bound with nucleic acid such as oligonucleotides, peptide analogs and cholesterols, as to be used in the gene relating technologies. In formula (1), R1, X, X', Y and n are the same as defined in the specification.(FR) La présente invention concerne de nouveaux dérivés de pyrrolizine de la formule (1), leurs sels ou leurs solvates, ainsi que l'utilisation de ces composés comme médicaments antitumoraux ou comme agents alkylants de l'ADN spécifiques de site dans les techniques génétiques. Les composés et leurs sels sont solubles dans des solvants miscibles à l'eau et stables dans le corps de manière qu'ils peuvent être utilisés comme médicaments antitumoraux, et ils peuvent en outre se lier de telle manière aux matériaux fixés à l'acide nucléique en un site spécifique, tels les oligonucléotides, les analogues peptidiques et les cholestérols, qu'ils peuvent être utilisés dans les techniques génétiques. Formule (1) dans laquelle R1, X, X', Y et n sont les mêmes, tels que définis dans la description.
• 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.