1,4,8,12-tetra(2-hydroxyethyl)-1,4,8,12-tetraaza-cyclopentadecane | 163434-13-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1,4,8,12-tetra(2-hydroxyethyl)-1,4,8,12-tetraaza-cyclopentadecane
• 英文别名: 2,2',2'',2'''-(1,4,8,12-Tetraazacyclopentadecane-1,4,8,12-tetrayl)tetra(ethan-1-ol)；2-[1,4,12-tris(2-hydroxyethyl)-1,4,8,12-tetrazacyclopentadec-8-yl]ethanol
• CAS: 163434-13-7
• 化学式: C₁₉H₄₂N₄O₄
• 分子量: 390.567
• InChiKey: WIHOLDKYLNDSGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  93.9
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,4,8,12-tetra(2-hydroxyethyl)-1,4,8,12-tetraaza-cyclopentadecane 在 氯化亚砜 作用下， 生成 1,4,8,12-tetra(2-chloroethyl)-1,4,8,12-tetraaza-cyclopentadecane dihydrochloride
  参考文献：
  名称：

  Synthesis of novel DNA cross-linking antitumour agents based on polyazamacrocycles

  摘要：

  We are seeking to develop more effective alkylating agents as antitumour agents. In previous work conformationally restricted nitrogen mustards were synthesised containing piperidine or pyrrolidine rings. The free bases were designed to be bifunctional alkylating agents via aziridinium ion formation and the effects of varying the distances between the two alkylating sites were studied. Some efficient cross-linkers of naked DNA were prepared but few of these compounds exhibited significant cytotoxicity in human tumour cells in vitro. We have extended this work by making tri- and tetra-azamacrocyclic compounds containing two to four potential alkylating sites. Most of these compounds were powerful DNA alkylating agents and showed cytotoxicity (IC(50) values 6-100 mu M) comparable with chlorambucil (45 mu M) and melphalan (8.5 mu M). In particular the cyclen derivative 2a was more than 10(4) times more effective at cross-linking DNA (2a XL(50) << 10 nM) than chlorambucil (XL(50) 100 mu M), and showed significant cytotoxicity in human tumour cells in vitro. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.055
• 作为产物：
  描述：

  环氧乙烷 、 1,4,8,12-四氮杂环十五烷 以 乙醇 为溶剂， 以86%的产率得到1,4,8,12-tetra(2-hydroxyethyl)-1,4,8,12-tetraaza-cyclopentadecane
  参考文献：
  名称：

  Synthesis of novel DNA cross-linking antitumour agents based on polyazamacrocycles

  摘要：

  We are seeking to develop more effective alkylating agents as antitumour agents. In previous work conformationally restricted nitrogen mustards were synthesised containing piperidine or pyrrolidine rings. The free bases were designed to be bifunctional alkylating agents via aziridinium ion formation and the effects of varying the distances between the two alkylating sites were studied. Some efficient cross-linkers of naked DNA were prepared but few of these compounds exhibited significant cytotoxicity in human tumour cells in vitro. We have extended this work by making tri- and tetra-azamacrocyclic compounds containing two to four potential alkylating sites. Most of these compounds were powerful DNA alkylating agents and showed cytotoxicity (IC(50) values 6-100 mu M) comparable with chlorambucil (45 mu M) and melphalan (8.5 mu M). In particular the cyclen derivative 2a was more than 10(4) times more effective at cross-linking DNA (2a XL(50) << 10 nM) than chlorambucil (XL(50) 100 mu M), and showed significant cytotoxicity in human tumour cells in vitro. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.055

文献信息

• Conjugated lipomers and uses thereof
  申请人：Massachusetts Institute of Technology

  公开号：US10933139B2

  公开（公告）日：2021-03-02

  The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

  本发明提供了创造性的共轭聚乙烯亚胺（PEI）聚合物和共轭杂大环（在此统称为 "共轭脂质体 "或 "脂质体"），它们含有一个或多个式(iii)基团： 其中 R3 和 R4 如本文所定义。此外，还提供了包含本发明共轭脂聚体的组合物，以及制备和使用方法。
• CONJUGATED LIPOMERS AND USES THEREOF
  申请人：Dahlman James E.

  公开号：US20120251560A1

  公开（公告）日：2012-10-04

  The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R 3 and R 4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.
• US9238716B2
  申请人：——

  公开号：US9238716B2

  公开（公告）日：2016-01-19
• [EN] CONJUGATED LIPOMERS AND USES THEREOF<br/>[FR] LIPOMÈRES CONJUGUÉS ET UTILISATIONS ASSOCIÉES
  申请人：MASSACHUSETTS INST TECHNOLOGY

  公开号：WO2012135025A2

  公开（公告）日：2012-10-04

  The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as "conjugated lipomers" or "lipomers") containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.
• Synthesis of novel DNA cross-linking antitumour agents based on polyazamacrocycles
  作者：Laurie L. Parker、Fiona M. Anderson、C. Caroline O’Hare、Stephen M. Lacy、John P. Bingham、David J. Robins、John A. Hartley

  DOI：10.1016/j.bmc.2005.01.055

  日期：2005.4

  We are seeking to develop more effective alkylating agents as antitumour agents. In previous work conformationally restricted nitrogen mustards were synthesised containing piperidine or pyrrolidine rings. The free bases were designed to be bifunctional alkylating agents via aziridinium ion formation and the effects of varying the distances between the two alkylating sites were studied. Some efficient cross-linkers of naked DNA were prepared but few of these compounds exhibited significant cytotoxicity in human tumour cells in vitro. We have extended this work by making tri- and tetra-azamacrocyclic compounds containing two to four potential alkylating sites. Most of these compounds were powerful DNA alkylating agents and showed cytotoxicity (IC(50) values 6-100 mu M) comparable with chlorambucil (45 mu M) and melphalan (8.5 mu M). In particular the cyclen derivative 2a was more than 10(4) times more effective at cross-linking DNA (2a XL(50) << 10 nM) than chlorambucil (XL(50) 100 mu M), and showed significant cytotoxicity in human tumour cells in vitro. (c) 2005 Elsevier Ltd. All rights reserved.