8-Chloro-2-fluoro-indolo[2,1-b]quinazoline-6,12-dione | 1421765-53-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-Chloro-2-fluoro-indolo[2,1-b]quinazoline-6,12-dione
• 英文别名: 8-chloro-2-fluoroindolo[2,1-b]quinazoline-6,12-dione
• CAS: 1421765-53-8
• 化学式: C₁₅H₆ClFN₂O₂
• 分子量: 300.676
• InChiKey: YMIRTWSSRVPVGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 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：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-Chloro-2-fluoro-indolo[2,1-b]quinazoline-6,12-dione 、 丙二腈 在 三乙胺 作用下， 以 乙腈 为溶剂， 以83 %的产率得到2-(8-chloro-2-fluoro-12-oxoindolo[2,1-b]quinazolin-6(12H)-ylidene)malononitrile
  参考文献：
  名称：

  色胺菊酯-丙二腈加合物用于苯胺的高效关闭荧光传感

  摘要：

  详细研究了苯胺对 2-(8-chloro-12-oxo-12 H -indolo[2,1- b ]quinazolin-6-ylidene)-malononitrile ( 5a ) 的荧光猝灭。时间相关单光子计数测量 (TCSPC) 表明猝灭涉及静态和动态机制，没有基态复杂的形成。在存在其他胺/芳烃的情况下对苯胺传感的选择性和抗干扰研究以及低 LOD 值表明5a作为苯胺传感分子探针的潜力，它也不受 pH 值变化的影响。

  DOI：

  10.1016/j.saa.2023.122755
• 作为产物：
  描述：

  5-氟靛红酸酐 、 5-氯靛红 在 三乙胺 作用下， 以 甲苯 为溶剂， 以76%的产率得到8-Chloro-2-fluoro-indolo[2,1-b]quinazoline-6,12-dione
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Tryptanthrins As Antitubercular Agents

  摘要：

  The natural product tryptanthrin (la) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.

  DOI：

  10.1021/np3007167

文献信息

• Design, Synthesis, and Structure–Activity Relationship Studies of Tryptanthrins As Antitubercular Agents
  作者：Jae-Min Hwang、Taegwon Oh、Takushi Kaneko、Anna M. Upton、Scott G. Franzblau、Zhenkun Ma、Sang-Nae Cho、Pilho Kim

  DOI：10.1021/np3007167

  日期：2013.3.22

  The natural product tryptanthrin (la) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.
• Tryptanthrin-malononitrile adduct for highly efficient turn-off fluorescent sensing of aniline
  作者：Haitham K.R. Al-Sharifi、Arsha Rajan、S.L. Sruthi、Ani Deepthi

  DOI：10.1016/j.saa.2023.122755

  日期：2023.9

  (5a) by aniline was studied in detail. Time correlated single photon counting measurements (TCSPC) indicated that the quenching involved both static and dynamic mechanisms without ground state complex formation. The selectivity towards aniline sensing in presence of other amines/aromatics and the anti-interference studies together with the low LOD value indicates the potential of 5a as a molecular probe

  详细研究了苯胺对 2-(8-chloro-12-oxo-12 H -indolo[2,1- b ]quinazolin-6-ylidene)-malononitrile ( 5a ) 的荧光猝灭。时间相关单光子计数测量 (TCSPC) 表明猝灭涉及静态和动态机制，没有基态复杂的形成。在存在其他胺/芳烃的情况下对苯胺传感的选择性和抗干扰研究以及低 LOD 值表明5a作为苯胺传感分子探针的潜力，它也不受 pH 值变化的影响。