(3-tert-BOCamino-propyl)-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester | 162339-83-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3-tert-BOCamino-propyl)-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester
• 英文别名: N-(2-hydroxyethyl)-N,N'-bis(tert-butyloxycarbonyl)-1,3-propanediamine；tert-butyl N-(3-{[(tert-butoxy)carbonyl]amino}propyl)-N-(2-hydroxyethyl)carbamate；tert-butyl N-(2-hydroxyethyl)-N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]carbamate
• CAS: 162339-83-5
• 化学式: C₁₅H₃₀N₂O₅
• 分子量: 318.414
• InChiKey: NPPBXIFQABPLRZ-UHFFFAOYSA-N

物化性质

• 沸点：
  441.3±38.0 °C(Predicted)
• 密度：
  1.072±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-tert-BOCamino-propyl)-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester 在 potassium carbonate 、 一水合肼 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 21.0h， 生成 6-{3-[2-(3-tert-BOCamino)-propyl-(tert-BOCamino)-ethylamino]-1-propyl}-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  内酰胺氮上具有多胺侧链的茚并异喹啉拓扑异构酶I抑制剂的设计，合成和生物学评估。

  摘要：

  茚并异喹啉类是一类非喜树碱拓扑异构酶I抑制剂，在人类癌细胞培养中表现出明显的细胞毒性。与喜树碱相比，它们具有许多潜在的优势，包括更高的化学稳定性，更持久的裂解复合物的形成以及DNA裂解位点独特模式的诱导。分子模型表明，茚并异喹啉内酰胺氮上的取代基将从三元裂解复合物中的DNA双链体中穿过主沟突出。这表明在该位置上相对较大的取代基将被耐受而不损害生物活性。作为提高茚并异喹啉的效力和潜在治疗作用的策略，合成了一系列在内酰胺氮上含有多胺侧链的化合物。合成这些化合物的基本原理是，带正电荷的铵阳离子通过与带负电荷的DNA主链的静电结合，可以增加DNA亲和力，并且多胺还可以通过利用多胺转运蛋白来促进细胞摄取。合成中的关键步骤涉及将含有受保护胺侧链的席夫碱与取代的邻苯二甲酸酐缩合，生成顺式-3-芳基-4-羧基-1-异喹啉酮。然后将这些异喹诺酮与亚硫酰氯转化为茚并异喹啉。尽管单胺比先导化合物更有效，通过在侧

  DOI：

  10.1021/jm030313f
• 作为产物：
  描述：

  2-羟乙胺丙胺 、 2-(叔丁氧羰基氧亚氨基)-2-苯乙腈 以 四氢呋喃 为溶剂， 反应 12.0h， 以58%的产率得到(3-tert-BOCamino-propyl)-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and radioprotective activity of WR-1065 derivatives: N-(2-acetylthioethyl)-1,3-propanediamine and N,N′-bis(2-acetylthioethyl)-1,3-propanediamine

  摘要：

  N-(2-Acetylthioethyl)-1,3-propanediamine (13a, as its 2HBr salt, or 13b, as its 2CF(3)CO(2)H salt) and N,N'-bis(2-acetyl-thioethyl)-1,3-propanediamine (16, as its 2CF(3)CO(2)H salt) have been prepared and evaluated as potential radioprotectors in mice. Their toxicity and radioprotective activity (survival rate) have been determined and compared with that of WR-2721. Intermediate N-(2-acetylthioethyl)-N,N'-bis(Z or Boc)-1,3-propanediamines were prepared in two ways from the corresponding alcohols. The most convenient method (the Mitsunobu procedure) was used to obtain the N,N'-bis(2-acetylthioethylated) derivative from the corresponding diol. Surprisingly, none of these compounds possesses radioprotective activity.

  DOI：

  10.1016/0223-5234(96)88208-0

文献信息

• [EN] MACROCYCLIC TGF-BR2 KINASE INHIBITORS<br/>[FR] INHIBITEURS MACROCYCLIQUES DE LA KINASE TGF-BR2
  申请人：ONCODESIGN SA

  公开号：WO2015136073A1

  公开（公告）日：2015-09-17

  The present invention relates to macrocyclic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of Transforming Growth Factor beta Receptor 2 (TGF-β R2) and/or mutants thereof, for use in the diagnosis, prevention and/or treatment of TGF-β R2 -kinase associated diseases. Moreover, the present invention provides methods of using said compounds, for instance as a medicine or diagnostic agent.

  本发明涉及大环化合物和含有该化合物的组合物，作为激酶抑制剂，特别是作为转化生长因子β受体2（TGF-β R2）及/或其突变体的抑制剂，用于诊断、预防和/或治疗TGF-β R2-激酶相关疾病。此外，本发明提供了使用该化合物的方法，例如作为药物或诊断试剂。
• Design, synthesis, and biological evaluation of cytotoxic 11-aminoalkenylindenoisoquinoline and 11-diaminoalkenylindenoisoquinoline topoisomerase I inhibitors
  作者：Xiangshu Xiao、Smitha Antony、Glenda Kohlhagen、Yves Pommier、Mark Cushman

  DOI：10.1016/j.bmc.2004.07.027

  日期：2004.10

  The cytotoxic indenoisoquinolines are a novel class of noncamptothecin topoisomerase I inhibitors having certain features that compare favorably with the camptothecins. A new strategy was adopted to attach aminoalkenyl substituents at C-11 of the indenoisoquinoline ring system, which, according to molecular modeling, would orient the side chains toward the DNA minor groove. All of the newly synthesized compounds were more cytotoxic than the parent indenoisoquinoline NSC 314622. Despite an imperfect correlation between cytotoxicities and topoisomerase I inhibition results, the hypothetical structural model of the cleavage complex presented here provides a conceptual framework to explain the structure-activity relationships. (C) 2004 Elsevier Ltd. All rights reserved.
• WO2023/86365
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Biological Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Featuring Polyamine Side Chains on the Lactam Nitrogen
  作者：Muthukaman Nagarajan、Xiangshu Xiao、Smitha Antony、Glenda Kohlhagen、Yves Pommier、Mark Cushman

  DOI：10.1021/jm030313f

  日期：2003.12.1

  persistent cleavage complexes, and induction of a unique pattern of DNA cleavage sites. Molecular modeling has suggested that substituents on the indenoisoquinoline lactam nitrogen would protrude out of the DNA duplex in the ternary cleavage complex through the major groove. This indicates that relatively large substituents in that location would be tolerated without compromising biological activity. As a

  茚并异喹啉类是一类非喜树碱拓扑异构酶I抑制剂，在人类癌细胞培养中表现出明显的细胞毒性。与喜树碱相比，它们具有许多潜在的优势，包括更高的化学稳定性，更持久的裂解复合物的形成以及DNA裂解位点独特模式的诱导。分子模型表明，茚并异喹啉内酰胺氮上的取代基将从三元裂解复合物中的DNA双链体中穿过主沟突出。这表明在该位置上相对较大的取代基将被耐受而不损害生物活性。作为提高茚并异喹啉的效力和潜在治疗作用的策略，合成了一系列在内酰胺氮上含有多胺侧链的化合物。合成这些化合物的基本原理是，带正电荷的铵阳离子通过与带负电荷的DNA主链的静电结合，可以增加DNA亲和力，并且多胺还可以通过利用多胺转运蛋白来促进细胞摄取。合成中的关键步骤涉及将含有受保护胺侧链的席夫碱与取代的邻苯二甲酸酐缩合，生成顺式-3-芳基-4-羧基-1-异喹啉酮。然后将这些异喹诺酮与亚硫酰氯转化为茚并异喹啉。尽管单胺比先导化合物更有效，通过在侧
• Synthesis and radioprotective activity of WR-1065 derivatives: N-(2-acetylthioethyl)-1,3-propanediamine and N,N′-bis(2-acetylthioethyl)-1,3-propanediamine
  作者：J Oiry、JY Pue、JD Laval、M Fatome、JL Imbach

  DOI：10.1016/0223-5234(96)88208-0

  日期：1995.1

  N-(2-Acetylthioethyl)-1,3-propanediamine (13a, as its 2HBr salt, or 13b, as its 2CF(3)CO(2)H salt) and N,N'-bis(2-acetyl-thioethyl)-1,3-propanediamine (16, as its 2CF(3)CO(2)H salt) have been prepared and evaluated as potential radioprotectors in mice. Their toxicity and radioprotective activity (survival rate) have been determined and compared with that of WR-2721. Intermediate N-(2-acetylthioethyl)-N,N'-bis(Z or Boc)-1,3-propanediamines were prepared in two ways from the corresponding alcohols. The most convenient method (the Mitsunobu procedure) was used to obtain the N,N'-bis(2-acetylthioethylated) derivative from the corresponding diol. Surprisingly, none of these compounds possesses radioprotective activity.