N-(6-chloro-2-methoxy-acridin-9-yl)-N'-[3-(6-chloro-2-methoxyacridin-9-ylamino)-propyl]-propane-1,3-diamine | 57735-82-7

• 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: N-(6-chloro-2-methoxy-acridin-9-yl)-N'-[3-(6-chloro-2-methoxyacridin-9-ylamino)-propyl]-propane-1,3-diamine
• 英文别名: 1,9-Bis-(2-methoxy-6-chlor-9-acridinyl)-1,5,9-triazanonan；1,3-Propanediamine, N-(6-chloro-2-methoxy-9-acridinyl)-N'-(3-((6-chloro-2-methoxy-9-acridinyl)amino)propyl)-；N'-(6-chloro-2-methoxyacridin-9-yl)-N-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]propane-1,3-diamine
• CAS: 57735-82-7
• 化学式: C₃₄H₃₃Cl₂N₅O₂
• 分子量: 614.574
• InChiKey: JXKNOHCXCIJXLN-UHFFFAOYSA-N

物化性质

• 熔点：
  157-159 °C
• 沸点：
  840.0±65.0 °C(Predicted)
• 密度：
  1.339±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  80.3
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(6-chloro-2-methoxy-acridin-9-yl)-N'-[3-(6-chloro-2-methoxyacridin-9-ylamino)-propyl]-propane-1,3-diamine 在 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-N,N-bis[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]propanamide
  参考文献：
  名称：

  Antimalarial, Antitrypanosomal, and Antileishmanial Activities and Cytotoxicity of Bis(9-amino-6-chloro-2-methoxyacridines):  Influence of the Linker

  摘要：

  Forty bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties are joined by alkanediamines, polyamines, or polyamines substituted by a side chain, were synthesized and tested for their in vitro activity upon the erythrocytic stage of Plasmodium falciparum, trypomastigote stage of Trypanosoma brucei, and amastigote stage of Trypanosoma cruzi and Leishmania infantum as well as for their cytotoxic effects upon MRC-5 cells. Results clearly showed the importance of the nature of the linker and of its side chain for antiparasitic activity, cytotoxicity, and cellular localization. Among several compounds devoid of cytotoxic effects at 25 mu M upon MRC-5 cells, one displayed IC50 values ranging from 8 to 18 nM against different P. falciparum strains while three others totally inhibited T. brucei at 1.56 mu M.

  DOI：

  10.1021/jm990946n
• 作为产物：
  描述：

  N-(6-Chloro-2-methoxy-acridin-9-yl)-N'-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-N'-((4S,5R,4'R)-2,2,2',2'-tetramethyl-[4,4']bi[[1,3]dioxolanyl]-5-ylmethyl)-propane-1,3-diamine 在 溶剂黄146 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 N-(6-chloro-2-methoxy-acridin-9-yl)-N'-[3-(6-chloro-2-methoxyacridin-9-ylamino)-propyl]-propane-1,3-diamine
  参考文献：
  名称：

  三胺连接吖啶二聚体的酸催化断裂反应

  摘要：

  描述了从 Nϵ-(2,3,4,5-四羟基戊基)取代的侧链和/或其丙酮化物形式的三胺连接的吖啶二聚体的 C-Nϵ键的酸催化裂解。提出了一种设想的多邻基辅助溶剂分解反应机理。

  DOI：

  10.1002/jccs.200100115

文献信息

• Linker-modified triamine-linked acridine dimers: Synthesis and cytotoxicity properties in vitro and in vivo
  作者：Shan-Shue Wang、Yi-Jen Lee、Shih-Chung Hsu、Hsueh-O Chang、Wei-Kung Yin、Lien-Shange Chang、Shan-Yen Chou

  DOI：10.1016/j.bmc.2006.10.054

  日期：2007.1

  preparation and cytotoxicity properties of a series of N(epsilon)-substituted triamine-linked acridine dimers are described. Most acridine dimer derivatives reveal highly potent in vitro cytotoxicity properties and DNA binding activity. Several acridine dimers were selected to study their action in vivo. These acridine dimers have demonstrated a narrow safe margin, as has adriamycin, but higher maximum

  描述了一系列N（ε）取代的三胺连接的a啶二聚体的制备和细胞毒性。大多数a啶二聚体衍生物具有很强的体外细胞毒性和DNA结合活性。选择了几种a啶二聚体以研究其在体内的作用。与阿霉素相比，这些demonstrated啶二聚体已显示出狭窄的安全范围，但与ICR小鼠中的阿霉素相比，其最大耐受剂量（MTD）更高。cr啶二聚体在体内还表现出各种抗anol-COLO 205实体肿瘤活性。化合物1显示出最有效的实体瘤抑制作用。
• Dimeric quinacrine derivatives as autophagy inhibitors for cancer therapy
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US10774047B2

  公开（公告）日：2020-09-15

  The invention provides dimeric quinacrine derivatives and related compounds and compositions, methods of treatment and syntheses. The novel compounds exhibit unexpected anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.

  本发明提供了二聚喹啉衍生物和相关化合物及组合物、治疗方法和合成方法。这些新型化合物具有意想不到的抗癌活性，可用于治疗多种自噬相关疾病。
• Increasing antitumor activity in vivo by enhancing acridine dimer solubility with salt preparations
  作者：Shan-Shue Wang、Yi-Jen Lee、Shih-Chung Hsu、Chen Hsieh、Lien-Shange Chang、Shan-Yen Chou

  DOI：10.1007/s00044-009-9213-9

  日期：2010.7

  The potent activities of many anticancer agents have been demonstrated by in vitro assays. However, their poor solubility may result in diminishing anticancer activities in vivo. Previously, we synthesized a series of bisacridine derivatives shown to be potent in cytotoxicity and DNA intercalating activity in vitro. Initially, the compound 1, (N-(6-chloro-2-methoxy-acridin-9-yl)-N'-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-propane-1,3-diamine), is insoluble in polar solvent and does not reveal antihuman COLO 205 solid-tumor activity in vivo. To enhance its solubility, three salt forms (CH(3)COOH, CH(3)SO(3)H, and CF(3)COOH) of compound 1 were synthesized and their solubility was found to be greatly improved compared with that of the free base. Among these salts, the compound 1 center dot A (tris)acetate salt has shown good solubility in H(2)O and 2.5% Cremophor (v/v) and demonstrated anti-COLO205 solid-tumor activity in vivo.
• ACHSON, R. M.;CONSTABLE, E. C.;WRIGHT, R. G. ,, MCR.;TAYLOR, G. N., J. CHEM. RES. MICROFICHE, 1983, N 1, 2-3
  作者：ACHSON, R. M.、CONSTABLE, E. C.、WRIGHT, R. G. ,, MCR.、TAYLOR, G. N.

  DOI：——

  日期：——
• DIMERIC QUINACRINE DERIVATIVES AS AUTOPHAGY INHIBITORS FOR CANCER THERAPY
  申请人：The Trustees of The University of Pennsylvania

  公开号：EP3283463B1

  公开（公告）日：2021-01-20