[2-(acridin-9-ylamino)-ethyl]-methyl-carbamic acid tert-butyl ester | 388574-67-2

• 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: [2-(acridin-9-ylamino)-ethyl]-methyl-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[2-(acridin-9-ylamino)ethyl]-N-methylcarbamate
• CAS: 388574-67-2
• 化学式: C₂₁H₂₅N₃O₂
• 分子量: 351.448
• InChiKey: BQJXZTRGIPQFAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [2-(acridin-9-ylamino)-ethyl]-methyl-carbamic acid tert-butyl ester 在 盐酸 、 溶剂黄146 、 氨 作用下， 生成 N¹-(acridin-9-yl)-N²-methylethane-1,2-diamine
  参考文献：
  名称：

  pH and thermo dual stimulus-responsive liposome nanoparticles for targeted delivery of platinum-acridine hybrid agent

  摘要：

  The complexes of the type [PtCl(L2)(ACRAMTU)](NO3)(2) (ACRAMTU=1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea) were synthesized: PT-ACRAMTU (1), L2 = ethane-1,2- diamine (en); PT(dach)-ACRAMTU (2), L2 =(1R, 2R)-1, 2-diaminocyclohexane (dach); PT(pda-OH)-ACRAMTU (3), L2 = 2-hydroxy-1, 3-propanediamine (pda-OH). The complexes containing diverse diamines exhibit different DNA binding capacity and cytotoxicity. Complex 3 shows excellent capability not only on the strongest non-cisplatin-type DNA damage, but also superior anticancer activity in NCI-H460 cells (IC50 = 0.23 +/- 0.05 mu M). For overcoming water insolubly and side effects, we encapsulated complex 3 into liposomes. PT@NPs were characterized in terms of particle size, morphology, drug loading capacity (DLC), encapsulation efficiency (EE) and stability. In vitro triggered release showed that the release of the platinum drug was steerable and the release rate was fast under low pH (< 7.0) and high temperature (> T-m = 41 degrees C). PT@NPs showed significant inhibitory effect in NCI-H460 cells. Flow cytometry analysis indicates G0/G1 phase arrest of cells treated with complex 3, whereas cells treated with cisplatin progress to G2/M of the cell cycle. The mechanistic differences validate that complex 3 is a potent anticancer agent superior than current clinical platinum-based therapies. PT@NPs have the potential in drug delivery systems (DDS) for non-small cell lung cancer (NSCLC) therapy.

  DOI：

  10.1016/j.lfs.2018.11.052
• 作为产物：
  描述：

  9-氯吖啶 以 四氢呋喃 为溶剂， 生成 [2-(acridin-9-ylamino)-ethyl]-methyl-carbamic acid tert-butyl ester
  参考文献：
  名称：

  pH and thermo dual stimulus-responsive liposome nanoparticles for targeted delivery of platinum-acridine hybrid agent

  摘要：

  The complexes of the type [PtCl(L2)(ACRAMTU)](NO3)(2) (ACRAMTU=1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea) were synthesized: PT-ACRAMTU (1), L2 = ethane-1,2- diamine (en); PT(dach)-ACRAMTU (2), L2 =(1R, 2R)-1, 2-diaminocyclohexane (dach); PT(pda-OH)-ACRAMTU (3), L2 = 2-hydroxy-1, 3-propanediamine (pda-OH). The complexes containing diverse diamines exhibit different DNA binding capacity and cytotoxicity. Complex 3 shows excellent capability not only on the strongest non-cisplatin-type DNA damage, but also superior anticancer activity in NCI-H460 cells (IC50 = 0.23 +/- 0.05 mu M). For overcoming water insolubly and side effects, we encapsulated complex 3 into liposomes. PT@NPs were characterized in terms of particle size, morphology, drug loading capacity (DLC), encapsulation efficiency (EE) and stability. In vitro triggered release showed that the release of the platinum drug was steerable and the release rate was fast under low pH (< 7.0) and high temperature (> T-m = 41 degrees C). PT@NPs showed significant inhibitory effect in NCI-H460 cells. Flow cytometry analysis indicates G0/G1 phase arrest of cells treated with complex 3, whereas cells treated with cisplatin progress to G2/M of the cell cycle. The mechanistic differences validate that complex 3 is a potent anticancer agent superior than current clinical platinum-based therapies. PT@NPs have the potential in drug delivery systems (DDS) for non-small cell lung cancer (NSCLC) therapy.

  DOI：

  10.1016/j.lfs.2018.11.052

文献信息

• Design, Synthesis, and Biological Activity of a Novel Non-Cisplatin-type Platinum−Acridine Pharmacophore
  作者：Elizabeth T. Martins、Hemanta Baruah、Jaroslaw Kramarczyk、Gilda Saluta、Cynthia S. Day、Gregory L. Kucera、Ulrich Bierbach

  DOI：10.1021/jm010293m

  日期：2001.12.1

  Platinum-acridine conjugates were prepared from [PtCl2(ethane-1,2-diamine)] and the novel acridinylthioureas MeHNC(S)NMeAcr (6) and MeHNC(S)NMe(CH2CH2)NHAcr (15) by replacing one chloro leaving group in the cisplatin analogue with thiourea sulfur. In HL-60 leukemia cells, IC50 values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 muM, respectively. In the ovarian cell lines 2008 and C13*, 16 was active at micromolar concentrations and showed only partial cross-resistance with clinical cisplatin. Possible structure-activity relationships are discussed.
• pH and thermo dual stimulus-responsive liposome nanoparticles for targeted delivery of platinum-acridine hybrid agent
  作者：Qian Zhou、Chaoqun You、Yang Ling、Hongshuai Wu、Baiwang Sun

  DOI：10.1016/j.lfs.2018.11.052

  日期：2019.1

  The complexes of the type [PtCl(L2)(ACRAMTU)](NO3)(2) (ACRAMTU=1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea) were synthesized: PT-ACRAMTU (1), L2 = ethane-1,2- diamine (en); PT(dach)-ACRAMTU (2), L2 =(1R, 2R)-1, 2-diaminocyclohexane (dach); PT(pda-OH)-ACRAMTU (3), L2 = 2-hydroxy-1, 3-propanediamine (pda-OH). The complexes containing diverse diamines exhibit different DNA binding capacity and cytotoxicity. Complex 3 shows excellent capability not only on the strongest non-cisplatin-type DNA damage, but also superior anticancer activity in NCI-H460 cells (IC50 = 0.23 +/- 0.05 mu M). For overcoming water insolubly and side effects, we encapsulated complex 3 into liposomes. PT@NPs were characterized in terms of particle size, morphology, drug loading capacity (DLC), encapsulation efficiency (EE) and stability. In vitro triggered release showed that the release of the platinum drug was steerable and the release rate was fast under low pH (< 7.0) and high temperature (> T-m = 41 degrees C). PT@NPs showed significant inhibitory effect in NCI-H460 cells. Flow cytometry analysis indicates G0/G1 phase arrest of cells treated with complex 3, whereas cells treated with cisplatin progress to G2/M of the cell cycle. The mechanistic differences validate that complex 3 is a potent anticancer agent superior than current clinical platinum-based therapies. PT@NPs have the potential in drug delivery systems (DDS) for non-small cell lung cancer (NSCLC) therapy.