{3,5-difluoro-4-[bis(2-hydroxyethyl)amino]phenyl}oxycarbonyladamantane | 694504-02-4

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: {3,5-difluoro-4-[bis(2-hydroxyethyl)amino]phenyl}oxycarbonyladamantane
• CAS: 694504-02-4
• 化学式: C₂₁H₂₇F₂NO₅
• 分子量: 411.446
• InChiKey: DOMSDLHUGDHZKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  79.23
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  {3,5-difluoro-4-[bis(2-hydroxyethyl)amino]phenyl}oxycarbonyladamantane 在 4-二甲氨基吡啶 、 甲酸 、 Amberlyst 27 resin 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 40.5h， 生成 (2S)-2-[[4-[bis(2-iodoethyl)amino]-3,5-difluorophenoxy]carbonylamino]hexanedioic acid
  参考文献：
  名称：

  Significant Differences in Biological Parameters between Prodrugs Cleavable by Carboxypeptidase G2 That Generate 3,5-Difluoro-phenol and -aniline Nitrogen Mustards in Gene-Directed Enzyme Prodrug Therapy Systems

  摘要：

  Nine new nitrogen mustard compounds derived from 2,6-difluoro-4-hydroxy- (3a-e) and 2,6-difluoro-4-amino- (4a-d) aniline were synthesized as potential prodrugs. They were designed to be activated to their corresponding 3,5-difluorophenol and -aniline (4)-nitrogen mustards by the enzyme carboxypeptidase G2 (CPG2) in gene-directed enzyme prodrug therapy (GDEPT) models. The compounds were tested for cytotoxicity in the MDA MB-361 breast adenocarcinoma. The cell line was engineered to express stably either CPG2 tethered to the cell surface stCPG2(Q)3 or beta-galactosidase (beta-Gal) as control. The cytotoxicity differentials were calculated between CPG 2-expressing and -nonexpressing cells and yielded different results for the two series of prodrugs despite their structural similarities. While the phenol compounds are ineffective as prodrugs, their aniline counterparts exhibit outstanding activity in the tumor cell lines expressing CPG2. {3,5-Difluoro-4-[bis(2-chloroethyl)amino]phenyl}carbamoyl-L-glutamic acid gave a differential of >227 in MDA MB361 cells as compared with 19 exhibited by 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid, 1a, which has been in clinical trials.

  DOI：

  10.1021/jm030966w
• 作为产物：
  描述：

  4-nitro-3,5-difluorophenyloxycarbonyladamantane 在 palladium on activated charcoal 甲酸铵 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 48.0h， 生成 {3,5-difluoro-4-[bis(2-hydroxyethyl)amino]phenyl}oxycarbonyladamantane
  参考文献：
  名称：

  Significant Differences in Biological Parameters between Prodrugs Cleavable by Carboxypeptidase G2 That Generate 3,5-Difluoro-phenol and -aniline Nitrogen Mustards in Gene-Directed Enzyme Prodrug Therapy Systems

  摘要：

  Nine new nitrogen mustard compounds derived from 2,6-difluoro-4-hydroxy- (3a-e) and 2,6-difluoro-4-amino- (4a-d) aniline were synthesized as potential prodrugs. They were designed to be activated to their corresponding 3,5-difluorophenol and -aniline (4)-nitrogen mustards by the enzyme carboxypeptidase G2 (CPG2) in gene-directed enzyme prodrug therapy (GDEPT) models. The compounds were tested for cytotoxicity in the MDA MB-361 breast adenocarcinoma. The cell line was engineered to express stably either CPG2 tethered to the cell surface stCPG2(Q)3 or beta-galactosidase (beta-Gal) as control. The cytotoxicity differentials were calculated between CPG 2-expressing and -nonexpressing cells and yielded different results for the two series of prodrugs despite their structural similarities. While the phenol compounds are ineffective as prodrugs, their aniline counterparts exhibit outstanding activity in the tumor cell lines expressing CPG2. {3,5-Difluoro-4-[bis(2-chloroethyl)amino]phenyl}carbamoyl-L-glutamic acid gave a differential of >227 in MDA MB361 cells as compared with 19 exhibited by 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid, 1a, which has been in clinical trials.

  DOI：

  10.1021/jm030966w