4-{4-[bis-(2-chloro-ethyl)-amino]-phenoxy}-butyric acid methyl ester | 500895-96-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-{4-[bis-(2-chloro-ethyl)-amino]-phenoxy}-butyric acid methyl ester
• 英文别名: 4-{4-[Bis-(2-chlor-aethyl)-amino]-phenoxy}-buttersaeure-methylester；Methyl 4-[4-[bis(2-chloroethyl)amino]phenoxy]butanoate
• CAS: 500895-96-5
• 化学式: C₁₅H₂₁Cl₂NO₃
• 分子量: 334.243
• InChiKey: DBFRFFOLQXXWJW-UHFFFAOYSA-N

物化性质

• 沸点：
  40-60 °C
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-{4-[bis-(2-chloro-ethyl)-amino]-phenoxy}-butyric acid methyl ester 在 盐酸 、 sodium azide 、 氯甲酸乙酯 、 三乙胺 作用下， 以 丙酮 、 苯 为溶剂， 反应 2.59h， 生成 4-(3-aminopropoxy)-N,N-bis(2-chloroethyl)aniline
  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：

  4-{4-[bis-(2-hydroxy-ethyl)-amino]-phenoxy}-butyric acid methyl ester 在 三氯氧磷 作用下， 生成 4-{4-[bis-(2-chloro-ethyl)-amino]-phenoxy}-butyric acid methyl ester
  参考文献：
  名称：

  Davis et al., Journal of the Chemical Society, 1955, p. 890,894

  摘要：

  DOI：

文献信息

• Davis et al., Journal of the Chemical Society, 1955, p. 890,894
  作者：Davis et al.

  DOI：——

  日期：——
• DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain
  作者：Kisione K. Valu、Trudi A. Gourdie、Theodore J. Boritzki、G. Lance Gravatt、Bruce C. Baguley、William R. Wilson、Laurence P. G. Wakelin、Paul D. Woodgate、William A. Denny

  DOI：10.1021/jm00173a016

  日期：1990.11

  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.