2-amino-5,10-dihydro-10-oxoimidazo<4,5-b>acridine hydrobromide | 142212-12-2

• 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-amino-5,10-dihydro-10-oxoimidazo<4,5-b>acridine hydrobromide
• 英文别名: 2-Amino-1,5-dihydroimidazo[4,5-b]acridin-10-one;hydrobromide
• CAS: 142212-12-2
• 化学式: BrH*C₁₄H₁₀N₄O
• 分子量: 331.172
• InChiKey: NLKDPOYEDQYPBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.72
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.8
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  溴化氰 、 2,3-diamino-9,10-dihydro-9-oxoacridine 以 二氯甲烷 为溶剂， 反应 72.0h， 以1.36 g的产率得到2-amino-5,10-dihydro-10-oxoimidazo<4,5-b>acridine hydrobromide
  参考文献：
  名称：

  HIV-1 neutralization and tumor cell proliferation inhibition in vitro by simplified analogs of pyrido[4,3,2-mn]thiazolo[5,4-b]acridine marine alkaloids

  摘要：

  The antiviral/antitumor marine alkaloid dercitin was used as a lead compound to design analogues with anti-HIV and tumor inhibitory activities. Deletion of structural features contributing to cytotoxicity led to analogues with lowered T-lymphocyte toxicity profiles. One compound, 5, induced complete protection against HIV-1 infectivity in vitro at 12.5-mu-g/mL (38-mu-M) without T-cell toxicity up to 400-mu-g/mL. Compound 4 and 5 also inhibited the binding of HIV-1 to H-9 lymphocytes. These compounds may exert antiviral activity by a unique dual extracellular and intracellular mode of action-both preventing viral attachment to lymphocytes as well as intercalating with viral nucleic acid. Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5-mu-M concentration compared to a 70-mu-M dose level of 5-fluorouracil. A means of molecular separation of antiviral activity from cytotoxicity was thus achieved, and putative pharmacophores for antiviral and antitumor actions of the prototype molecule dercitin have been deduced. The 2-thio-9-acridinone derivatives 4 and 5 represent a new structural type exhibiting activity against HIV in vitro, serving as chemical leads in the design of anti-AIDS agents, while thiazolo[5,4-b]acridines such as 2 provide leads in the drug design of new antitumor agents.

  DOI：

  10.1021/jm00093a005

文献信息

• HIV-1 neutralization and tumor cell proliferation inhibition in vitro by simplified analogs of pyrido[4,3,2-mn]thiazolo[5,4-b]acridine marine alkaloids
  作者：Irach B. Taraporewala、James W. Cessac、Tran C. Chanh、Angel V. Delgado、Raymond F. Schinazi

  DOI：10.1021/jm00093a005

  日期：1992.7

  The antiviral/antitumor marine alkaloid dercitin was used as a lead compound to design analogues with anti-HIV and tumor inhibitory activities. Deletion of structural features contributing to cytotoxicity led to analogues with lowered T-lymphocyte toxicity profiles. One compound, 5, induced complete protection against HIV-1 infectivity in vitro at 12.5-mu-g/mL (38-mu-M) without T-cell toxicity up to 400-mu-g/mL. Compound 4 and 5 also inhibited the binding of HIV-1 to H-9 lymphocytes. These compounds may exert antiviral activity by a unique dual extracellular and intracellular mode of action-both preventing viral attachment to lymphocytes as well as intercalating with viral nucleic acid. Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5-mu-M concentration compared to a 70-mu-M dose level of 5-fluorouracil. A means of molecular separation of antiviral activity from cytotoxicity was thus achieved, and putative pharmacophores for antiviral and antitumor actions of the prototype molecule dercitin have been deduced. The 2-thio-9-acridinone derivatives 4 and 5 represent a new structural type exhibiting activity against HIV in vitro, serving as chemical leads in the design of anti-AIDS agents, while thiazolo[5,4-b]acridines such as 2 provide leads in the drug design of new antitumor agents.