<(10-cyclopropyl-9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid | 142212-11-1

• 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: <(10-cyclopropyl-9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid
• 英文别名: 2-(10-Cyclopropyl-9-oxo-acridin-2-yl)sulfanylacetic acid；2-(10-cyclopropyl-9-oxoacridin-2-yl)sulfanylacetic acid
• CAS: 142212-11-1
• 化学式: C₁₈H₁₅NO₃S
• 分子量: 325.388
• InChiKey: NPQVIIUKPXVFHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 sodium hydroxide 、 sodium hydride 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 为溶剂， 反应 5.5h， 生成 <(10-cyclopropyl-9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid
  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.