4-(4-(N,N-bis(2-chloroethyl)amino)phenyl)butanal | 64977-05-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(4-(N,N-bis(2-chloroethyl)amino)phenyl)butanal
• 英文别名: 4-(4-(bis(2-chloroethyl)amino)phenyl)butanal；Benzenebutanal, 4-[bis(2-chloroethyl)amino]-；4-[4-[bis(2-chloroethyl)amino]phenyl]butanal
• CAS: 64977-05-5
• 化学式: C₁₄H₁₉Cl₂NO
• 分子量: 288.217
• InChiKey: HUIZMVVIRCIOPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-(N,N-bis(2-chloroethyl)amino)phenyl)butanal 在 盐酸羟胺 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 0.42h， 以98%的产率得到N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylimine
  参考文献：
  名称：

  Assessment of Chemoselective Neoglycosylation Methods Using Chlorambucil as a Model

  摘要：

  To systematically assess the impact of glycosylation and the corresponding chemoselective linker upon the anticancer activity/selectivity of the drug chlorambucil, herein we report the synthesis and anticancer activities of a 63-member library of chlorambucil-based neoglycosides. A comparison of N-alkoxyamine-. N-acylhydrazine-, and N-hydroxyamine-based chemoselective glycosylation of chlorambucil revealed sugar- and linker-dependent partitioning among open- and closed-ring neoglycosides and corresponding sugar-dependent variant biological activity. Cumulatively, this study represents the First neoglycorandomization of a synthetic drug and expands our understanding of the impact of sugar structure upon product distribution/equilibria in the context of N-alkoxyamino-, N-hydroxyamino-, and N-acylhydrazine-based chemoselective glycosylation. This study also revealed several analogues with increased in vitro anticancer activity, most notably D-threoside 60 (NSC 748747), which displayed much broader tumor specificity and notably increased potency over the parent drug.

  DOI：

  10.1021/jm101024j
• 作为产物：
  描述：

  苯丁酸氮芥 在 草酰氯 、 dimethyl sulfide borane 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.25h， 生成 4-(4-(N,N-bis(2-chloroethyl)amino)phenyl)butanal
  参考文献：
  名称：

  DNA定向烷基化剂。6.苯并咪唑的DNA小沟靶向苯胺芥子类似物的合成及其抗肿瘤活性（Hoechst 33258）

  摘要：

  已合成了一系列的DNA小沟结合荧光团苯甲酰氮的芥末氮类似物（Hoechst 33258），并评估了其抗肿瘤活性。通过两个连续的Pinner型反应，从哌嗪基末端按常规方法构建双苯并咪唑环系统，使被2-甲基类似物污染的产物收率低，这证明很难分离。已开发出另一种合成方法，包括从芥末末端构建双苯并咪唑，通过芥末醛与3,4-二氨基苄腈的Cu（2+）促进的氧化偶联反应形成单苯并咪唑，然后进行Pinner型反应和缩合反应用4-（1-甲基-4-哌嗪基）-邻苯二胺。此过程可提供更高的产量和纯净的产品。芥末类似物表现出高脱敏因子（IC50AA8 / IC50 UV4），这是DNA烷化剂的典型特征。在整个同源序列中，细胞毒性的增加很大（85倍），这不能完全由芥子反应性的变化来解释，并且可能与芥子相对于DNA的方向改变有关，从而导致烷基化的方式不同。使用单剂量方案，苯甲酸对苯二酚本身（已在临床上作为抗癌药进行评估

  DOI：

  10.1021/jm00051a010

文献信息

• MODIFIED CYTOTOXINS AND THEIR THERAPEUTIC USE
  申请人：The Regents of the University of California

  公开号：US20170080094A1

  公开（公告）日：2017-03-23

  The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.

  本公开通常提供了用于治疗癌症的化合物。在某些方面，本公开提供了经化学修饰以包含一个或多个包含疏水部分的基团的小分子细胞毒素。在某些实施例中，本公开提供了经含脂肪酸基团化学修饰的小分子细胞毒素。在某些方面，本公开提供了包括这种修饰的小分子细胞毒素和蛋白质的组合物，例如制药组合物。在某些实施例中，蛋白质是白蛋白或类白蛋白。此外，本公开提供了这些化合物和组合物的各种用途。
• DNA-targeted alkylating agents
  申请人：Auckland Division Cancer Society of New Zealand Inc.

  公开号：US05968933A1

  公开（公告）日：1999-10-19

  The invention relates to novel bis-benzimidazole compounds which have the ability to bind to the minor groove of DNA and to alkylate DNA, to methods of preparing the compounds, and the use of the compounds in the treatement of neoplastic disease.

  这项发明涉及一种新型的双苯并咪唑化合物，该化合物具有结合DNA小沟和烷基化DNA的能力，以及制备这些化合物的方法，以及在治疗肿瘤性疾病中使用这些化合物的方法。
• GLYCOSYLATED CHLORAMBUCIL ANALOGS AND USES THEREOF
  申请人：Thorson Jon S.

  公开号：US20120094946A1

  公开（公告）日：2012-04-19

  A library of glycosylated chlorambucil analogs which are useful as anti-tumor and/or anti-metastatic agents is disclosed. The glycosylated chlorambucil analogs have the general formula wherein represents a reducing sugar moiety.

  揭示了一种作为抗肿瘤和/或抗转移药物有用的葡萄糖基氯氨丁醇类似物的图书馆。这些葡萄糖基氯氨丁醇类似物具有一般公式，其中表示还原糖基团。
• Modified cytotoxins and their therapeutic use
  申请人：The Regents of the University of California

  公开号：US10023581B2

  公开（公告）日：2018-07-17

  The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.

  本公开内容一般提供用于治疗癌症的化合物。在某些方面，本公开提供的小分子细胞毒素经过化学修饰，包括一个或多个含有疏水部分的分子。在一些实施方案中，本公开提供了用含脂肪酸的分子进行化学修饰的小分子细胞毒素。在某些方面，本公开提供的组合物，如药物组合物，包括这种修饰的小分子细胞毒素和蛋白质。在某些实施方案中，蛋白质是白蛋白或白蛋白模拟物。此外，本公开还提供了这些化合物和组合物的各种用途。
• Anti-cancer compounds
  申请人：Stewart M. John

  公开号：US20060183772A1

  公开（公告）日：2006-08-17

  The invention provides bradykinin antagonists and pharmaceutically acceptable salts thereof having anti-cancer activity. These anti-cancer compounds are particularly useful for inhibiting the growth of lung and prostate cancers.

  本发明提供了具有抗癌活性的缓激肽拮抗剂及其药学上可接受的盐类。这些抗癌化合物特别适用于抑制肺癌和前列腺癌的生长。