<(9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid | 126862-63-3

• 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: <(9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid
• 英文别名: (9,10-dihydro-9-oxo-acridin-2-ylthio)acetic acid；2-[(9-oxo-10H-acridin-2-yl)sulfanyl]acetic acid
• CAS: 126862-63-3
• 化学式: C₁₅H₁₁NO₃S
• 分子量: 285.323
• InChiKey: WFJQKCGOMANRBI-UHFFFAOYSA-N

物化性质

• 熔点：
  288-291 °C (decomp)
• 沸点：
  525.0±50.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <(9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid 在 sodium hydroxide 、 sodium hydride 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 6.0h， 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
• 作为产物：
  描述：

  2-(4-甲氧基苯氨基)-苯甲酸 在 环丁砜 、 sodium hydroxide 、 硫酸 、 sodium hydride 作用下， 以 乙醇 、 水 为溶剂， 反应 30.33h， 生成 <(9,10-dihydro-9-oxo-2-acridinyl)thio>acetic acid
  参考文献：
  名称：

  抗炎9,10-二氢-9-氧代-2-A啶烷-链烷酸和4-（2-羧苯基）氨基苯链烷酸的合成及构效关系

  摘要：

  制备了三个化学系列的18种测试化合物作为潜在的抗炎药，并通过大鼠后足角叉菜胶诱导的水肿试验进行了评估。具有已知消炎和抗过敏性环加氧酶和脂氧合酶抑制剂的等排化合物是10-甲基-9,10-二氢-9-氧代-2-ac啶烷酸，9,10-二氢-9-氧代-2-酸cr啶链烷酸和4-（2-羧基苯基）氨基苯链烷酸。这些系列中的每一个中的化合物的链烷酸侧链结构均不同。含有乙酸和支链2-丙酸侧链的化合物显示出角叉菜胶诱导的水肿的抑制作用。具有这些侧链的化合物的活性，以及​​与羧基，氧乙酸，硫代乙酸，3-丙酸侧链与Appleton和Brown提出的模板模型有关的环加氧酶的活性位点相一致，而不是由Gund和Shen提出的替代活性位点模型。一种化合物（+-）-2- [N-（2-羧基苯基）-4-氨基苯基]丙酸（3c）在50 mg / kg po时表现出水肿抑制作用，其等效剂量水平为（+ ）萘普生。含有羧酸侧链的化合物4a

  DOI：

  10.1002/jps.2600790219

文献信息

• TARAPOREWALA, IRACH B.;KAUFFMAN, JOEL M., J. PHARM. SCI., 79,(1990) N, C. 173-178
  作者：TARAPOREWALA, IRACH B.、KAUFFMAN, JOEL M.

  DOI：——

  日期：——
• Synthesis and Structure–Activity Relationships of Anti-inflammatory 9,lO-Dihydro-9-oxo-2-Acridine-alkanoic Acids and 4-(2-Carboxyphenyl)aminobenzenealkanoic Acids
  作者：Irach B. Taraporewala、Joel M. Kauffman

  DOI：10.1002/jps.2600790219

  日期：1990.2

  prepared as potential anti-inflammatory agents and evaluated by the rat hindpaw carrageenan-induced edema assay. The compounds, isosteric with known anti-inflammatory and antiallergic cyclo-oxygenase and lipoxygenase inhibitors, are 10-methyl-9,10-dihydro-9-oxo-2-acridinealkanoic acids, 9,10-dihydro-9-oxo-2-acridinealkanoic acids, and 4-(2-carboxyphenyl)aminobenzenealkanoic acids. Compounds within each

  制备了三个化学系列的18种测试化合物作为潜在的抗炎药，并通过大鼠后足角叉菜胶诱导的水肿试验进行了评估。具有已知消炎和抗过敏性环加氧酶和脂氧合酶抑制剂的等排化合物是10-甲基-9,10-二氢-9-氧代-2-ac啶烷酸，9,10-二氢-9-氧代-2-酸cr啶链烷酸和4-（2-羧基苯基）氨基苯链烷酸。这些系列中的每一个中的化合物的链烷酸侧链结构均不同。含有乙酸和支链2-丙酸侧链的化合物显示出角叉菜胶诱导的水肿的抑制作用。具有这些侧链的化合物的活性，以及​​与羧基，氧乙酸，硫代乙酸，3-丙酸侧链与Appleton和Brown提出的模板模型有关的环加氧酶的活性位点相一致，而不是由Gund和Shen提出的替代活性位点模型。一种化合物（+-）-2- [N-（2-羧基苯基）-4-氨基苯基]丙酸（3c）在50 mg / kg po时表现出水肿抑制作用，其等效剂量水平为（+ ）萘普生。含有羧酸侧链的化合物4a
• 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.