8-Chloro-10b-hydroindolino[1,2-a]pyridino[4,3-d]pyrimidine-6,11-dione | 169039-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 8-Chloro-10b-hydroindolino[1,2-a]pyridino[4,3-d]pyrimidine-6,11-dione
• 英文别名: 14-chloro-2,6,10-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1,3(8),4,6,11(16),12,14-heptaene-9,17-dione
• CAS: 169039-08-1
• 化学式: C₁₄H₆ClN₃O₂
• 分子量: 283.674
• InChiKey: QSBNOGVVXYQZLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 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：
  62.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-Chloro-10b-hydroindolino[1,2-a]pyridino[4,3-d]pyrimidine-6,11-dione 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成
  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
• 作为产物：
  描述：

  4-氨基吡啶-3-羧酸 在 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 24.0h， 生成 8-Chloro-10b-hydroindolino[1,2-a]pyridino[4,3-d]pyrimidine-6,11-dione
  参考文献：
  名称：

  作为新型抗植物病原体细菌剂的有效杀菌剂的发现和作用机制

  摘要：

  色胺菊酯及其衍生物是天然生物碱，具有广泛的生物活性。本研究采用抗植物病原体的缩合环化反应制备了4个系列的含4-aza/3-aza/2-aza/1-aza色胺菊酯的氮杂色胺酮衍生物，开发了一种新型天然产物型细菌农药。化合物4Aza-8对轴突黄单胞菌pv的致病菌表现出显着的生长抑制作用。柑橘( Xac ),米黄单胞菌pv。Oryzae ( Xoo ) 和Pseudomonas syringae pv。猕猴桃( Psa) 最终校正后的 EC 50值分别为 0.312、1.91 和 18.0 μg/mL，大大优于色胺酮 (Tryp)。此外，4Aza-8在体内对柑橘溃疡病也显示出有效的治疗和保护活性。对Xac 的进一步机制研究表明化合物4Aza-8能够影响Xac的生长曲线和生物膜的形成，导致细菌形态严重收缩，增加活性氧水平，并诱导细菌细胞凋亡。对差异蛋白谱的定量分析发现，主要差异主要集中在细菌分泌系

  DOI：

  10.1021/acs.jafc.3c01120

文献信息

• 氮杂色胺酮类衍生物的合成及在防治植物病原菌细菌、真菌杀菌剂及抗植物病毒制剂的应用
  申请人：贵州大学

  公开号：CN114805353A

  公开（公告）日：2022-07-29

  本发明公开了系列取代的氮杂色胺酮类衍生物，所发明的化合物作为防治植物病原菌细菌、真菌杀菌剂及抗植物病毒制剂的用途，所述衍生物的通式如(I)所示，其中，各取代基的定义详见说明书。该通式所示的化合物对植物病原菌细菌如水稻白叶枯病、真菌如稻瘟病具有较高的杀菌活性和抗植物病毒活性，可用于制备农用特效杀菌剂和抗烟草花叶病毒制剂；
• 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.
• Discovery and Mechanism of Azatryptanthrin Derivatives as Novel Anti-Phytopathogenic Bacterial Agents for Potent Bactericide Candidates
  作者：Guanglong Zhang、Chengpeng Li、Yan Li、Danping Chen、Zhuirui Li、Guiping Ouyang、Zhenchao Wang

  DOI：10.1021/acs.jafc.3c01120

  日期：2023.4.26

  transport and affected the transfer of DNA to the host cell. In summary, these research results suggest that 4Aza-8 represents a promising anti-phytopathogenic-bacteria agent, which is worth being further investigated as a bactericide candidate.

  色胺菊酯及其衍生物是天然生物碱，具有广泛的生物活性。本研究采用抗植物病原体的缩合环化反应制备了4个系列的含4-aza/3-aza/2-aza/1-aza色胺菊酯的氮杂色胺酮衍生物，开发了一种新型天然产物型细菌农药。化合物4Aza-8对轴突黄单胞菌pv的致病菌表现出显着的生长抑制作用。柑橘( Xac ),米黄单胞菌pv。Oryzae ( Xoo ) 和Pseudomonas syringae pv。猕猴桃( Psa) 最终校正后的 EC 50值分别为 0.312、1.91 和 18.0 μg/mL，大大优于色胺酮 (Tryp)。此外，4Aza-8在体内对柑橘溃疡病也显示出有效的治疗和保护活性。对Xac 的进一步机制研究表明化合物4Aza-8能够影响Xac的生长曲线和生物膜的形成，导致细菌形态严重收缩，增加活性氧水平，并诱导细菌细胞凋亡。对差异蛋白谱的定量分析发现，主要差异主要集中在细菌分泌系