1-[(2Z)-(4-(5-bromouracil-1-yl)but-2-enyl)]-5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinolin-2,2-dioxide | 1262035-45-9

• 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: 1-[(2Z)-(4-(5-bromouracil-1-yl)but-2-enyl)]-5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinolin-2,2-dioxide
• 英文别名: 5-bromo-1-[(Z)-4-(2,2-dioxo-2λ6-thia-1,3-diazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-3-yl)but-2-enyl]pyrimidine-2,4-dione
• CAS: 1262035-45-9
• 化学式: C₁₇H₁₇BrN₄O₄S
• 分子量: 453.316
• InChiKey: SZVGFWQEBHHYCG-UPHRSURJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  98.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 1-[(Z)-(4-(thymin-1-yl)but-2-enyl)]-5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinolin-2,2-dioxide 在 sodium iodide 作用下， 以 乙腈 为溶剂， 以295 mg的产率得到1-[(2Z)-(4-(5-bromouracil-1-yl)but-2-enyl)]-5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinolin-2,2-dioxide
  参考文献：
  名称：

  Design, synthesis and inhibitory activity against Mycobacterium tuberculosis thymidine monophosphate kinase of acyclic nucleoside analogues with a distal imidazoquinolinone

  摘要：

  Thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt) has been proposed as an attractive target in the search of new agents to fight against tuberculosis. We recently reported that thymine derivatives carrying a naphtholactam or naphthosultam moiety at position 4 of a (Z)-butenyl chain inhibit TMPKmt in the sub mu M range. Here we describe the replacement of the planar naphtholactam and naphthosultam rings in our identified hits by 5,6-dihydro-1H-imidazo[4,5,1-ij]quinolinones and a 5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinoline-2,2-dioxide where the planarity has been broken. Interestingly, these non-planar compounds were similarly potent against the target enzyme than their aromatic analogues, suggesting a bioisosteric behavior that may also be applied to other biologically active compounds. The synthesis of the different targeted imidazoquinolinones has been successfully performed via a hypervalent iodide mediated oxidative cyclization of N-methoxyureas catalized by bis(trifluoroacetoxy)iodobenzene (PIFA) expanding the reported use of this reagent for the synthesis of differently substituted imidazoquinolinones. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.09.056

文献信息

• Design, synthesis and inhibitory activity against Mycobacterium tuberculosis thymidine monophosphate kinase of acyclic nucleoside analogues with a distal imidazoquinolinone
  作者：Olga Familiar、Hélène Munier-Lehmann、José Antonio Aínsa、María-José Camarasa、María-Jesús Pérez-Pérez

  DOI：10.1016/j.ejmech.2010.09.056

  日期：2010.12

  Thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt) has been proposed as an attractive target in the search of new agents to fight against tuberculosis. We recently reported that thymine derivatives carrying a naphtholactam or naphthosultam moiety at position 4 of a (Z)-butenyl chain inhibit TMPKmt in the sub mu M range. Here we describe the replacement of the planar naphtholactam and naphthosultam rings in our identified hits by 5,6-dihydro-1H-imidazo[4,5,1-ij]quinolinones and a 5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinoline-2,2-dioxide where the planarity has been broken. Interestingly, these non-planar compounds were similarly potent against the target enzyme than their aromatic analogues, suggesting a bioisosteric behavior that may also be applied to other biologically active compounds. The synthesis of the different targeted imidazoquinolinones has been successfully performed via a hypervalent iodide mediated oxidative cyclization of N-methoxyureas catalized by bis(trifluoroacetoxy)iodobenzene (PIFA) expanding the reported use of this reagent for the synthesis of differently substituted imidazoquinolinones. (C) 2010 Elsevier Masson SAS. All rights reserved.