{4-[tert-butoxycarbonyl-(4-oxo-butyl)-amino]-butyl}-carbamic acid tert-butyl ester | 876757-72-1

• 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: {4-[tert-butoxycarbonyl-(4-oxo-butyl)-amino]-butyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]-N-(4-oxobutyl)carbamate
• CAS: 876757-72-1
• 化学式: C₁₈H₃₄N₂O₅
• 分子量: 358.478
• InChiKey: JYADDDUVEOJUOV-UHFFFAOYSA-N

物化性质

• 沸点：
  478.6±38.0 °C(Predicted)
• 密度：
  1.035±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  阿霉素 、 {4-[tert-butoxycarbonyl-(4-oxo-butyl)-amino]-butyl}-carbamic acid tert-butyl ester 在 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (4-((tert-butoxycarbonyl)amino)butyl)(4-(((2S,3S,4S,6R)-3-hydroxy-2-methyl-6-(((1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl)oxy)tetrahydro-2H-pyran-4-yl)amino)butyl)carbamate
  参考文献：
  名称：

  Compounds and method for enhancing the efficacy of anti-cancer drugs

  摘要：

  提供了聚胺化合物、用于抗癌目的的合成方法和使用方法，以及用于增强现有抗癌药物活性的方法。本公开揭示了可以附着在毒性剂上的某些聚胺基团，以促进它们进入癌细胞，以及在杀灭癌细胞方面具有惊人细胞毒性和选择性的聚胺化合物。其中包括具有三胺或四胺附加到细胞毒性剂的示例的插图结合系统。有五种示例性的方法方案说明了本发明化合物的合成。其中包括通过附着聚胺引导系统来增强细胞摄取的一般策略，其中包括将三胺引导附着到现有抗癌药物以提高其化疗效力的示例。有一个示例说明了使用三胺引导来提高蒽甲基胺类细胞毒性剂的选择性（例如，蒽甲基-4,4-三胺共轭物优于蒽甲基N-丁基胺衍生物）。还有一个示例说明了一种合成方法，用于将聚胺引导附着到现有的化疗药物多柔比星上。这种方法可以导致聚胺-多柔比星共轭物的合成。还有合成各种烷基芳基取代的聚胺、羟基化聚胺衍生物和环己基二胺类似物的插图。

  公开号：

  US07001925B1
• 作为产物：
  描述：

  在 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 ammonium hydroxide 、 碘苯二乙酸 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、2.03 MPa 条件下， 反应 37.0h， 生成 {4-[tert-butoxycarbonyl-(4-oxo-butyl)-amino]-butyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Biological Properties of Quilamines II, New Iron Chelators with Antiproliferative Activities

  摘要：

  To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.

  DOI：

  10.1021/bc4004734

文献信息

• Polyamine conjugates as selective NMDA inhibitors and anti-cancer drugs
  申请人：Phanstiel Otto

  公开号：US20070088081A1

  公开（公告）日：2007-04-19

  Polyamine compounds, method of synthesis and method of use for anti-cancer purposes, for enhancing the activity of existing anti-cancer drugs, as well as, for inhibiting N-Methyl-D-Aspartate (NMDA) receptors found in neurotransmission systems are provided. Certain polyamine motifs have been identified that can be attached to toxic agents to facilitate their access to cancer cells as well as polyamine compounds of surprising cytotoxicity with selectivity in killing cancer cells, and surprising utility in the treatment of Alzheimer's disease and brain stroke. It includes an illustrative conjugate system with examples of a triamine or a tetraamine appended to a cytotoxic agent. Included is a general strategy to enhance cell uptake by attaching a polyamine vectoring system with an example of a triamine vector attached to an existing anti-cancer drug to improve its chemotherapeutic potency. There is an illustration of tetraamine derivatives which have surprising enhanced selectivity in inhibiting N-methyl-D-aspartate (NMDA) receptors involved in neurotransmission. Several ligands can affect the activity of this receptor, which has been shown to initiate cell death under stroke conditions (lack of oxygen). Tetraamine derivatives which bind or inhibit the action of the NMDA receptor provide new therapy for NMDA-associated human diseases, such as Alzheimer's disease and stroke.

  提供聚胺化合物的合成方法和用于抗癌目的的使用方法，用于增强现有抗癌药物的活性，以及用于抑制神经递质系统中发现的N-甲基-D-天门冬氨酸（NMDA）受体。已经确定了某些聚胺基团，可以附加到毒性剂上，以促进它们进入癌细胞，以及具有惊人的细胞毒性选择性杀死癌细胞的聚胺化合物，并在阿尔茨海默病和脑卒中治疗方面具有惊人的实用价值。它包括一个具有三胺或四胺附加到细胞毒性剂的示例的说明性共轭系统。包括一般策略，通过附加聚胺矢量系统来增强细胞摄取，其中包括一个三胺矢量附加到现有抗癌药物上的示例，以提高其化疗效力。有一个四胺衍生物的示例，其在抑制神经递质中涉及的N-甲基-D-天门冬氨酸（NMDA）受体的选择性增强方面具有惊人的效果。几种配体可以影响该受体的活性，已经证明在缺氧的情况下引起细胞死亡。结合或抑制NMDA受体作用的四胺衍生物为NMDA相关的人类疾病提供了新的治疗方法，例如阿尔茨海默病和中风。
• US7001925B1
  申请人：——

  公开号：US7001925B1

  公开（公告）日：2006-02-21
• US7728040B1
  申请人：——

  公开号：US7728040B1

  公开（公告）日：2010-06-01
• Compounds and method for enhancing the efficacy of anti-cancer drugs
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：US07001925B1

  公开（公告）日：2006-02-21

  Polyamine compounds, method of synthesis and method of use for anti-cancer purposes, and for enhancing the activity of existing anti-cancer drugs are provided. This disclosure has identified certain polyamine motifs that can be attached to toxic agents to facilitate their access to cancer cells as well as polyamine compounds of surprising cytotoxicity and selectivity in killing cancer cells. It includes an illustrative conjugate system with examples of a triamine or a tetraamine appended to a cytotoxic agent. There are five method schemes illustrative of the synthesis of the compounds of the invention. Included is a general strategy to enhance cell uptake by attaching a polyamine vectoring system with an example of a triamine vector attached to an existing anti-cancer drug to improve its chemotherapeutic potency. There is an illustration of using the triamine vector to improve the selectivity of an anthracenylmethyl amine cytotoxic agent (e.g. an anthracenylmethyl-4,4-triamine conjugate outperformed an anthracenylmethyl N-butyl amine derivative). There is an illustration of a synthetic method to attach the polyamine vector onto an existing chemotherapeutic, doxorubicin. This methodology can lead to the synthesis of the polyamine-doxorubicin conjugate. There are illustrations of the synthesis of various alkyl aryl substituted polyamines, a hydroxylated polyamine derivative and a cyclohexyldiamine analogue.

  提供了聚胺化合物、用于抗癌目的的合成方法和使用方法，以及用于增强现有抗癌药物活性的方法。本公开揭示了可以附着在毒性剂上的某些聚胺基团，以促进它们进入癌细胞，以及在杀灭癌细胞方面具有惊人细胞毒性和选择性的聚胺化合物。其中包括具有三胺或四胺附加到细胞毒性剂的示例的插图结合系统。有五种示例性的方法方案说明了本发明化合物的合成。其中包括通过附着聚胺引导系统来增强细胞摄取的一般策略，其中包括将三胺引导附着到现有抗癌药物以提高其化疗效力的示例。有一个示例说明了使用三胺引导来提高蒽甲基胺类细胞毒性剂的选择性（例如，蒽甲基-4,4-三胺共轭物优于蒽甲基N-丁基胺衍生物）。还有一个示例说明了一种合成方法，用于将聚胺引导附着到现有的化疗药物多柔比星上。这种方法可以导致聚胺-多柔比星共轭物的合成。还有合成各种烷基芳基取代的聚胺、羟基化聚胺衍生物和环己基二胺类似物的插图。
• Synthesis and Biological Properties of Quilamines II, New Iron Chelators with Antiproliferative Activities
  作者：Vincent Corcé、Stéphanie Renaud、Isabelle Cannie、Karine Julienne、Sébastien G. Gouin、Olivier Loréal、François Gaboriau、David Deniaud

  DOI：10.1021/bc4004734

  日期：2014.2.19

  To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.