3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid | 92019-83-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid
• 英文别名: Propionic acid, 3-(p-(bis(2-chloroethyl)amino)phenoxy)-；3-[4-[bis(2-chloroethyl)amino]phenoxy]propanoic acid
• CAS: 92019-83-5
• 化学式: C₁₃H₁₇Cl₂NO₃
• 分子量: 306.189
• InChiKey: AAVIPUSYYJOCPI-UHFFFAOYSA-N

物化性质

• 熔点：
  93 °C
• 沸点：
  455.0±45.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid 在 盐酸 、 sodium azide 、 氯甲酸乙酯 、 三乙胺 作用下， 以 甲醇 、 丙酮 、 苯 为溶剂， 反应 25.92h， 生成 N-(2-(4-(Bis(2-chloroethyl)amino)phenoxy)ethyl)-9-acridinamine
  参考文献：
  名称：

  DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain

  摘要：

  Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.

  DOI：

  10.1021/jm00173a016
• 作为产物：
  描述：

  methyl 3-(4-nitrophenoxy)propionate 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙酸乙酯 、 苯 为溶剂， 反应 49.67h， 生成 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid
  参考文献：
  名称：

  DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain

  摘要：

  Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.

  DOI：

  10.1021/jm00173a016

文献信息

• [EN] ESTERS OF STEROIDAL LACTAM AND BIS(2-CHLOROETHYL) AMINOPHENOXY PROPANOIC ACID DERIVATIVES<br/>[FR] ESTERS DE LACTAME STÉROÏDE ET DÉRIVÉS D'ACIDE BIS (2-CHLOROÉTHYL)AMINOPHÉNOXY PROPANOÏQUE
  申请人：GALENICA S A

  公开号：WO2017001439A1

  公开（公告）日：2017-01-05

  Novel homo-aza-steroidal esters with alkylating bis(2-chloroethyl)aminophenoxy propanoic acid and substituted derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.

  新型的同型氮类类固醇酯化物，含有烷基化的双(2-氯乙基)氨基苯氧丙酸及其取代衍生物，其制备方法，含有它们的药物组合物，以及它们在癌症治疗中的应用。
• Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics
  作者：Dimitrios Trafalis、Elena Geromichalou、Panagiotis Dalezis、Nikolaos Nikoleousakos、Vasiliki Sarli

  DOI：10.1016/j.steroids.2016.07.009

  日期：2016.11

  Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo.

  如今，烷基化剂仍然是最重要的细胞毒性药物之一，其显示出广泛的治疗用途，可用于治疗各种癌症。我们已经合成和测试了四种杂合的氮杂氮杂甾类烷基化酯，它们对五种对烷基化剂，人白血病细胞系体外敏感，以及对P388鼠类白血病的体内抗白血病活性具有抗白血病作用。比较地，还研究了美法仑和3-（4-（双（2-氯乙基）氨基）苯氧基）丙酸（POPAM）。在体外和体内，所有的均氮-氮杂-甾族烷烃都显示出较低的急性毒性，非常有希望的抗白血病活性。
• Esters of steroidal lactam and bis(2-chloroethyl) aminophenoxy propanoic acid derivatives
  申请人：GALENICA S.A.

  公开号：US10208083B2

  公开（公告）日：2019-02-19

  Novel homo-aza-steroidal esters with alkylating bis(2-chloroethyl)aminophenoxy propanoic acid and substituted derivatives, processes for their preparation, pharmaceutical compositions containing them and use thereof in the treatment of cancer.

  具有烷基化作用的双(2-氯乙基)氨基苯氧基丙酸的新型均氮甾醇酯及其取代衍生物、其制备工艺、含有它们的药物组合物以及它们在治疗癌症中的用途。
• Davis et al., Journal of the Chemical Society, 1955, p. 890,894
  作者：Davis et al.

  DOI：——

  日期：——
• VALU, KISIONE K.;GOURDIE, TRUDI A.;BORITZKI, THEODORE J.;GRAVATT, G. LANC+, J. MED. CHEM., 33,(1990) N1, C. 3014-3019
  作者：VALU, KISIONE K.、GOURDIE, TRUDI A.、BORITZKI, THEODORE J.、GRAVATT, G. LANC+

  DOI：——

  日期：——