N/[3-(dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}-butyramide | 269402-54-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N/[3-(dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}-butyramide
• 英文别名: N-[3-(dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}butyramide；N-[3-(Dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}-butyramide；4-[4-[bis(2-chloroethyl)amino]phenyl]-N-[3-(dimethylamino)propyl]butanamide
• CAS: 269402-54-2
• 化学式: C₁₉H₃₁Cl₂N₃O
• 分子量: 388.381
• InChiKey: BKXUSRDLWLUHSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N/[3-(dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}-butyramide 、 碘甲烷 以 乙醇 为溶剂， 反应 3.0h， 以91%的产率得到{3-[(4-{4-[bis(2-chloroethyl)amino]phenyl}butanoyl)amino]propyl}trimethylammonium iodide
  参考文献：
  名称：

  Quaternary ammonium compounds

  摘要：

  具有与化学式（Ia）或（Ib）相对应的化合物： 其中： M代表可用于治疗或诊断由对软骨的攻击引起的病理的分子， R1、R2和R3代表烷基基团，或R1、R2和R3与携带它们的氮原子一起形成杂环， X代表（C1-C6）烷基链，其中一个或多个—CH2—基团可以选择性地被硫原子、氧原子或—NR—、—CO—、—CO—NH—、—CO2—、—SO—或—SO2—基团所取代， n代表0或1， Hal代表卤素原子， 或， R4代表烷基基团， Hal代表卤素原子， 代表可用于治疗或诊断由对软骨的攻击引起的病理的分子，其中氮原子可以选择性地包含在饱和或不饱和的含氮杂环系统中，或包含在双键中；以及其药物组成物。

  公开号：

  US06759406B1
• 作为产物：
  描述：

  苯丁酸氮芥 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 生成 N/[3-(dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}-butyramide
  参考文献：
  名称：

  Synthesis and in Vitro Evaluation of Quaternary Ammonium Derivatives of Chlorambucil and Melphalan, Anticancer Drugs Designed for the Chemotherapy of Chondrosarcoma

  摘要：

  To enhance affinity for malignant cartilaginous tumors (chondrosarcomas), quaternary ammonium (QA) conjugates of chlorambucil and melphalan were prepared by linking the QA moiety to nitrogen mustards via an amide bond. They exhibited closely similar and sometimes more favorable values than their parent compounds. In the cell lines tested, the two QA conjugates displayed appreciable cytotoxicity, the QA conjugate of chlorambucil even showing an enhanced efficiency against chondrosarcoma compared with chlorambucil.

  DOI：

  10.1021/jm010926x

文献信息

• New quaternary ammonium compounds
  申请人：——

  公开号：US20040208822A1

  公开（公告）日：2004-10-21

  A compound of formula corresponding to either formula (Ia) or (Ib): 1 wherein: M represents a molecule that can be used for the treatment or diagnosis of pathologies caused by attack on the cartilage, R 1 , R 2 and R 3 represent alkyl, or R 1, R 2 and R 3 together with the nitrogen atom carrying them, form a heterocycle, X represents a (C 1 -C 6 )alkylene chain in which one or more —CH 2 — groups are optionally replaced by sulphur, oxygen, or —NR—, —CO—, —CO—NH—, —CO 2 —, —SO— or —SO 2 —, n represents 0 or 1, Hal represents halogen, or, 2 R 4 represents alkyl, Hal represents halogen, 3 represents a molecule that can be used for the treatment or diagnosis of pathologies caused by attack on the cartilage, wherein the nitrogen atom may optionally be included in a saturated or unsaturated nitrogen-containing heterocyclic system, or included in a double bond.

  化合物的化学式对应于公式(Ia)或(Ib)中的任意一种： 其中， M代表可用于治疗或诊断由对软骨的攻击引起的病理的分子， R1、R2和R3代表烷基，或者R1、R2和R3连同它们携带的氮原子形成一个杂环， X代表一个(C1-C6)烷基链，其中一个或多个—CH2—基团可选择地被硫、氧、—NR—、—CO—、—CO—NH—、—CO2—、—SO—或—SO2—取代， n代表0或1， Hal代表卤素， 或者， 2R4代表烷基， Hal代表卤素， 3代表可用于治疗或诊断由对软骨的攻击引起的病理的分子，其中氮原子可选择地包括在饱和或不饱和的含氮杂环系统中，或包括在双键中。
• Synthesis and pharmacokinetic profile of a quaternary ammonium derivative of chlorambucil, a potential anticancer drug for the chemotherapy of chondrosarcoma
  作者：Maryse Rapp、Isabelle Giraud、Jean-Claude Maurizis、Jean-Claude Madelmont

  DOI：10.1016/j.bmc.2003.09.006

  日期：2003.11

  As a part of our targeting program based on the affinity of the quaternary ammonium moiety for cartilage, our objective was to develop more selective anticancer drugs towards chondrosarcoma that would concentrate in this malignant cartilaginous tissue and so improve the therapeutic index through a reduction of side effects. For this purpose we have synthesized and labeled with C-14 a quaternary ammonium (QA) derivative of chlorambucil. Biological studies performed in rats showed that [C-14]-CQA and [C-14]-chlorambucil exhibited different pharmacokinetic profiles. The blood elimination of [C-14]-CQA was faster than that of parent compound. [C-14]-CQA was principally excreted by the fecal way. However, until 15 min after administration, levels of radioactivity were measured in cartilaginous tissues of rats given [C-14]-CQA which was not the case for the rats which had received [C-14]-chlorambucil. Although rates of radioactivity were quantified only during 15 min, these results prove that the functionalization of chlorambucil by a quaternary ammonium group allows the molecule to be carried selectively to cartilaginous tissues. (C) 2003 Elsevier Ltd. All rights reserved.
• US6559125B1
  申请人：——

  公开号：US6559125B1

  公开（公告）日：2003-05-06
• US6759406B1
  申请人：——

  公开号：US6759406B1

  公开（公告）日：2004-07-06
• US7008613B2
  申请人：——

  公开号：US7008613B2

  公开（公告）日：2006-03-07