4-[4-[Bis(2-chloroethyl)amino]phenyl]sulfanylaniline | 133041-87-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-[4-[Bis(2-chloroethyl)amino]phenyl]sulfanylaniline
• CAS: 133041-87-9
• 化学式: C₁₆H₁₈Cl₂N₂S
• 分子量: 341.304
• InChiKey: QKEKHMCYHYNORZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯喹啉 、 4-[4-[Bis(2-chloroethyl)amino]phenyl]sulfanylaniline 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 4-喹啉胺,N-[4-[[4-[二(2-氯乙基)氨基]苯基]硫代]苯基]-
  参考文献：
  名称：

  DNA-directed alkylating agents. 4. 4-Anilinoquinoline-based minor groove directed aniline mustards

  摘要：

  A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor groove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for cytotoxicity to correlate with mustard reactivity, this was much less pronounced than with untargeted mustards. The compounds were much more cytotoxic than the parent diols, and were at least 10-fold more cytotoxic than the corresponding aniline mustards themselves. Comparative cell line studies suggested that the mechanism of cytotoxicity varied with mustard reactivity. The most reactive mustards cross-linked DNA, while cell killing by the less reactive compounds appeared to be by the formation of bulky monoadducts. The compounds were active but not particularly dose-potent against P388 leukemia in vivo. The modest potency may be related to their poor aqueous solubility, since the more soluble methyl quaternary salts were equally active at much lower doses.

  DOI：

  10.1021/jm00109a005
• 作为产物：
  描述：

  4-nitrophenyl 4'-phenyl sulfide 在 盐酸 、 铁粉 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 0.92h， 生成 4-[4-[Bis(2-chloroethyl)amino]phenyl]sulfanylaniline
  参考文献：
  名称：

  Sulfoxide-Containing Aromatic Nitrogen Mustards as Hypoxia-Directed Bioreductive Cytotoxins

  摘要：

  A series of diaryl and alkylaryl sulfoxide-containing nitrogen mustards were synthesized and evaluated for their hypoxia-selective cytotoxicity against V-79 cells in vitro as well as for their metabolism profiles with the rat S-9 fractions. In general, the diaryl sulfoxides (4, 5, and 7-9) showed much greater hypoxia selectivity (11-27-fold) than the alkylaryl sulfoxides (similar to3-fold) (1 and 3). The fused diphenyl sulfoxides (10 and 11), on the other hand, showed very low hypoxia selectivity (1.3-3-fold). Compound 10 was highly cytotoxic under both aerobic and anaerobic conditions, while 11 showed low cytotoxicity under both conditions. The bioreduction of 8 by the rat S-9 fraction under anaerobic conditions was inhibited by menadione and enhanced by benzaldehyde, acetaldehyde, or 2-hydroxypyrimidine suggesting the involvement of aldehyde oxidase in the reduction of the sulfoxides. Bioreductive metabolism studies of selected model sulfoxides suggested that diaryl sulfoxides are better substrates for aldehyde oxidase than alkylaryl sulfoxides.

  DOI：

  10.1021/jm9904957

文献信息

• GRAVATT, G. LANCE;BAGULEY, BRUCE C.;WILSON, WILLIAM R.;DENNY, WILLIAM A., J. MED. CHEM., 34,(1991) N, C. 1552-1560
  作者：GRAVATT, G. LANCE、BAGULEY, BRUCE C.、WILSON, WILLIAM R.、DENNY, WILLIAM A.

  DOI：——

  日期：——
• [EN] SULFOXIDE DERIVATIVES OF NITROGEN-MUSTARD AND ANTICANCER AGENT CONTAINING THE SAME<br/>[FR] DERIVES SULFOXYDES DE L'YPERITE AZOTEE ET AGENT ANTICANCEREUX LES CONTENANT
  申请人：CHONG KUN DANG CORP.

  公开号：WO1997013748A1

  公开（公告）日：1997-04-17

  (EN) According to the present invention, are provided sulfoxide derivatives of nitrogen-mustard represented by general formula (I), wherein R1 represents a hydrogen, or haloethyl; R2 represents a lower alkyl or phenyl group substituted or non-substituted; and X represents a halogen atom. Provided that R1 is a chloroethyl and X is a chlorine, R2 does not represent methyl group; and an anticancer agent comprising the same as a prodrug. The sulfoxide derivatives according to the present invention convert to a sulfide in a hypoxic condition to show cytotoxicity, so that it is very useful as an anticancer agent selectively functions on a solid cancer which is in a hypoxic condition.(FR) La présente invention concerne des dérivés sulfoxydes de l'ypérite azotée, représentés par la formule générale (I) dans laquelle R1 représente un hydrogène ou un haloéthyle; R2 représente un groupe alkyle ou phényle inférieur, substitué ou non, et X représente un atome d'halogène. A condition que R1 soit un chloroéthyle et X un chlore, R2 ne représente pas un groupe méthyle. L'invention concerne aussi un agent anticancéreux contenant un de ces constituants en tant que promédicament. Les dérivés sulfoxydes selon l'invention se transforment en sulfure dans des conditions hypoxiques, faisant alors preuve de cytotoxicité, de telle sorte qu'ils sont très utiles comme agents anticancéreux qui agissent de manière sélective sur les cancers dans des conditions hypoxiques.
• DNA-directed alkylating agents. 4. 4-Anilinoquinoline-based minor groove directed aniline mustards
  作者：G. Lance Gravatt、Bruce C. Baguley、William R. Wilson、William A. Denny

  DOI：10.1021/jm00109a005

  日期：1991.5

  A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor groove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for cytotoxicity to correlate with mustard reactivity, this was much less pronounced than with untargeted mustards. The compounds were much more cytotoxic than the parent diols, and were at least 10-fold more cytotoxic than the corresponding aniline mustards themselves. Comparative cell line studies suggested that the mechanism of cytotoxicity varied with mustard reactivity. The most reactive mustards cross-linked DNA, while cell killing by the less reactive compounds appeared to be by the formation of bulky monoadducts. The compounds were active but not particularly dose-potent against P388 leukemia in vivo. The modest potency may be related to their poor aqueous solubility, since the more soluble methyl quaternary salts were equally active at much lower doses.
• Sulfoxide-Containing Aromatic Nitrogen Mustards as Hypoxia-Directed Bioreductive Cytotoxins
  作者：Zhong-Yue Sun、Emad Botros、Ai-Duen Su、Yu Kim、Enju Wang、Nesrine Z. Baturay、Chul-Hoon Kwon

  DOI：10.1021/jm9904957

  日期：2000.11.1

  A series of diaryl and alkylaryl sulfoxide-containing nitrogen mustards were synthesized and evaluated for their hypoxia-selective cytotoxicity against V-79 cells in vitro as well as for their metabolism profiles with the rat S-9 fractions. In general, the diaryl sulfoxides (4, 5, and 7-9) showed much greater hypoxia selectivity (11-27-fold) than the alkylaryl sulfoxides (similar to3-fold) (1 and 3). The fused diphenyl sulfoxides (10 and 11), on the other hand, showed very low hypoxia selectivity (1.3-3-fold). Compound 10 was highly cytotoxic under both aerobic and anaerobic conditions, while 11 showed low cytotoxicity under both conditions. The bioreduction of 8 by the rat S-9 fraction under anaerobic conditions was inhibited by menadione and enhanced by benzaldehyde, acetaldehyde, or 2-hydroxypyrimidine suggesting the involvement of aldehyde oxidase in the reduction of the sulfoxides. Bioreductive metabolism studies of selected model sulfoxides suggested that diaryl sulfoxides are better substrates for aldehyde oxidase than alkylaryl sulfoxides.