(3-(acridin-9-ylamino)-5-{2-[bis(2-chloroethyl)amino]ethoxy}phenyl)methanol | 774234-08-1

• 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-{2-[bis(2-chloroethyl)amino]ethoxy}phenyl)methanol
• 英文别名: Benzenemethanol, 3-(9-acridinylamino)-5-(2-(bis(2-chloroethyl)amino)ethoxy)-；[3-(acridin-9-ylamino)-5-[2-[bis(2-chloroethyl)amino]ethoxy]phenyl]methanol
• CAS: 774234-08-1
• 化学式: C₂₆H₂₇Cl₂N₃O₂
• 分子量: 484.425
• InChiKey: SRZKWNZALGFBCW-UHFFFAOYSA-N

物化性质

• 熔点：
  153-154 °C(Solv: acetone (67-64-1); hexane (110-54-3))
• 沸点：
  602.4±55.0 °C(Predicted)
• 密度：
  1.318±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.6
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

BO-0742是AHMA和N-芥末的衍生物，是一种有效的抗癌剂。研究显示，BO-0742能显著抑制小鼠体内的人类乳腺癌和卵巢癌异种移植肿瘤的生长。

反应信息

• 作为产物：
  描述：

  9-氯吖啶 在 盐酸 、 potassium fluoride 、 potassium carbonate 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3-(acridin-9-ylamino)-5-{2-[bis(2-chloroethyl)amino]ethoxy}phenyl)methanol
  参考文献：
  名称：

  Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation

  摘要：

  A series of 9-anilinoacridine N-mustard derivatives, in which the alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene spacer, was synthesized and evaluated for cytotoxicity against human lymphoblastic leukemic cells (CCRF-CEM) in culture. The results showed that all of the new compounds exhibited potent cytotoxicity with IC50 values ranging from 0.002 to 0.7 muM, which were as potent or significantly more potent than 3-(9-acridinylamino)-5-hydroxy-methylaniline (AHMA). Compound 9 did not exhibit cross-resistance against both vinblastine-resistant (CCRF-CEM/VBL) and taxol-resistant (CCRF-CEM/taxol) cells. Additionally, compound 9 demonstrated potent antitumor effect in nude mice bearing human breast carcinoma MX-1 xenografts, resulting in complete tumor remission in two out of three mice at the maximal dose of 1-2 mg/kg (Q3Dx7) or 3 mg/kg (Q4Dx5) via intravenous injection. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.080

文献信息

• 9-anilinoacridine alkylating agents
  申请人：Su Tsann-Long

  公开号：US20080176889A1

  公开（公告）日：2008-07-24

  This invention relates to 9-anilinoacridine alkylating agents, their synthesis and their use in pharmaceutical compositions for treating diseases.

  这项发明涉及9-苯胺基吖啶烷基化剂，它们的合成以及它们在治疗疾病的药物组合物中的应用。
• 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。
• PHENYL N-MUSTARD LINKED TO DNA-AFFINIC MOLECULES OR WATER-SOLUBLE ARYL RINGS, METHOD AND THEIR USE AS CANCER THERAPEUTIC AGENTS
  申请人：SU Tsann-Long

  公开号：US20130178494A1

  公开（公告）日：2013-07-11

  The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.

  本公开涉及新的DNA定向烷基化剂和具有改善化学稳定性和抗肿瘤治疗效果的水溶性N-芥子剂。
• Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity
  作者：Valeriy A. Bacherikov、Ting-Chao Chou、Hua-Jin Dong、Xiuguo Zhang、Ching-Huang Chen、Yi-Wen Lin、Tsong-Jen Tsai、Rong-Zau Lee、Leroy F. Liu、Tsann-Long Su

  DOI：10.1016/j.bmc.2005.03.057

  日期：2005.6

  A series of N-mustard derivatives of 9-anilinoacridine was synthesized for antitumor and structure-activity relationship studies. The alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene (O-C-2) O-butylene (O-C-4), and methylene (C-1) spacer. All of the new N-mustard derivatives exhibited significant cytotoxicity in inhibiting human lymphoblastic leukemic cells (CCRF-CEM) in culture. Of these agents, (3-(acridin-9-ylamino)-5-2-[bis(2-chloroethyl)amino]ethoxy}phenyl)methanol (10) was subjected to antitumor studies, resulting in an approximately 100-fold more potent effect than its parent analogue 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) in inhibiting the growth of human lymphoblastic leukemic cells (CCRF-CEM) in vitro. This agent did not exhibit cross-resistance against vinblastine-resistant (CCRF-CEM/VBL) or Taxol-resistant (CCRF-CEM/Taxol) cells. Remarkably, the therapeutic effect of 10 at a dose as low as one tenth of the Taxol therapeutic dose [i.e., 1-2 mg/kg (Q3D x 7) or 3 mg/kg (Q4D x 5); intravenous injection] on nude mice bearing human breast carcinoma MX-1 xenografts resulted in complete tumor remission in two out of three mice. Furthermore, 10 yielded xenograft tumor suppression of 81-96% using human T-cell acute lymphoblastic leukemia CCRF-CEM, colon carcinoma HCT-116, and ovarian adenocarcinoma SK-OV-3 tumor models. (c) 2005 Elsevier Ltd. All rights reserved.
• US8222297B2
  申请人：——

  公开号：US8222297B2

  公开（公告）日：2012-07-17