(3-(acridin-9-ylamino)-5-{4-[bis(2-chloroethyl)amino]phenylcarbamoyloxymethyl}phenyl)carbamic acid isobutyl ester | 1038623-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (3-(acridin-9-ylamino)-5-{4-[bis(2-chloroethyl)amino]phenylcarbamoyloxymethyl}phenyl)carbamic acid isobutyl ester
• 英文别名: 2-methylpropyl N-[3-(acridin-9-ylamino)-5-[[4-[bis(2-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenyl]carbamate
• CAS: 1038623-08-3
• 化学式: C₃₆H₃₇Cl₂N₅O₄
• 分子量: 674.627
• InChiKey: BBTXHFUBPYCGNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  p-isocyanophenyl mustard 、 [3-(acridin-9-ylamino)-5-hydroxymethylphenyl]carbamic acid isobutyl ester 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 以0.158 g的产率得到(3-(acridin-9-ylamino)-5-{4-[bis(2-chloroethyl)amino]phenylcarbamoyloxymethyl}phenyl)carbamic acid isobutyl ester
  参考文献：
  名称：

  Novel DNA-directed alkylating agents: Design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker

  摘要：

  A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies revealed that these derivatives possessed significant cytotoxicity with IC50 in sub-micromolar range in inhibiting human lymphoblastic leukemia (CCRF-CEM), breast carcinoma (MX-1), colon carcinoma (HCT-116) and human non-small cell lung cancer (H1299) cell growth in vitro. Compounds 10a, 10b, 10e, 10i, and 15a were selected for evaluating their antitumor activity in nude mice bearing MX1 and HCT-116 xenografts. Remarkably, total tumor remission was achieved by these agents with only one cycle of treatment. Interestingly, no tumor relapse was found in mice treated with 10a over 129 days. This agent is capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells in a dose dependent manner by modified comet assay and has a long half-life in rat plasma. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.022

文献信息

• Aniline or phenol mustards linked to DNA-affinic molecules or water-soluble aromatic rings and their use as cancer therapeutic agents
  申请人：Su Tsann-Long

  公开号：US20080171765A1

  公开（公告）日：2008-07-17

  New aniline or phenol N-mustards linked to DNA-affinity carriers (such as 9-anilinoacridines, acridines and quinolines), aminobenzamides or aminophenol ethers by a urea, carbamic acid, carbanic acid ester, hydrazineurea, hydrazinecarbamic acid ester, phenoxyurea, phenoxycarbamic acid ester linkage with improved chemical stability and anti-tumor therapeutic efficacy are provided.

  提供了与DNA亲和载体（如9-苯胺基吖啶、吖啶和喹啉）、氨基苯甲酰胺或氨基酚醚通过脲、碳酸酯、碳酸酯、叠氮脲、叠氮碳酸酯、苯氧基脲、苯氧基碳酸酯链接的新苯胺或酚N-芥子素，具有改善的化学稳定性和抗肿瘤治疗效果。
• US8222297B2
  申请人：——

  公开号：US8222297B2

  公开（公告）日：2012-07-17