8-iodinotryptanthrin

• 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-iodinotryptanthrin
• 英文别名: 8-iodoindolo[2,1-b]quinazoline-6,12-dione
• 化学式: C₁₅H₇IN₂O₂
• 分子量: 374.137
• InChiKey: BBGAOZGNPWPXNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  49.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-iodinotryptanthrin 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以72%的产率得到8-iodo-6-hydrazonoindolo[2,1-b]quinazolin-12(6H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 8-substituted-6-hydrazonoindolo[2,1- b ]quinazolin-12(6 H )-one scaffolds as potential cytotoxic agents: IDO-1 targeting molecular docking studies

  摘要：

  Herein, we have reported the synthesis of 18 novel 8-substituted tryptanthrin analogues based on our earlier work. All these tryptanthrin analogues were well characterized by H-1 & C-13 NMR, FT-IR, Mass Spectrometry and Elemental Analysis. All these 8-substituted analogues were screened for their anti-oxidant activity by DPPH radical scavenging assay. Out of all the tested compounds, T-11, T-12,T-17 and T-18 showed potent anti-oxidant activity. The anti-cancer activity have been performed by using MTT assay protocol and their results depicts that compounds having the 4-pyridyl or 4-carboxyphenyl substituents at the 8th position of the tryptanthrin framework are found to be the most promising cytotoxic agent against A549, MCF-7 and HeLa human cancer cell lines compared to others as well as with the standard drug cisplatin. Moreover, the comparative molecular docking studies against the three protein receptors IDO1, EGFR and HER2 strongly suggested that IDO1 is the best target protein, which exhibits lowest binding energies of -11.73 and -11.61 kcal mol(-1) for T-11 and T-12 scaffolds, respectively towards the in vitro anti-cancer activity. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.064
• 作为产物：
  描述：

  5-碘吲哚醌 、 靛红酸酐 在 N-甲基吗啉 、 吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 反应 6.0h， 生成 8-iodinotryptanthrin
  参考文献：
  名称：

  Cytotoxicity and reversal of multidrug resistance by tryptanthrin-derived indoloquinazolines

  摘要：

  评估一系列吲哚喹唑啉类化合物作为新型抗癌剂的效果并阐明其作用机制。将取代的异酸酐与取代的靛红进行缩合，制备出化合物 1â4 ，然后加入丙二腈，制备出化合物 5â7 。细胞毒性通过 MTT 试验测定。凋亡诱导采用 DNA 断裂、细胞周期测定、caspase 3/7 活性和 Western 印迹法进行评估。化合物 3、4 和 5 对 MCF-7、HeLa、SKOV3 和 A498 癌细胞具有细胞毒性。经化合物 3、4 和 5 处理的细胞出现 DNA 梯状。其中，化合物 4 在细胞周期的亚 G1 累积和 caspase-3/7 激活方面表现出最大的活性。此外，化合物 4 还提高了 Fas 和 Fas 配体的水平，这意味着细胞凋亡部分是通过信号介导的。另一方面，化合物 1 和 7 显示出化疗增敏活性，因为在 MCF-7/adr（对多柔比星耐药）和 MCF-7/vp（对依托泊苷耐药）中，多柔比星和依托泊苷的细胞毒性分别与化合物 1 和 7 结合使用时会增强。吲哚喹唑啉类化合物的细胞毒性是结构依赖性的，而不是细胞类型依赖性的，这是因为单个化合物在所有四种细胞系中诱导的细胞毒性程度相似。要开发出对 MCF-7 细胞具有细胞毒性或可逆转 MCF-7/adr 和 MCF-7/vp 耐药性的新型抗癌剂，进一步修饰胰黄素骨架非常重要。

  DOI：

  10.1038/aps.2009.198

文献信息

• Indolo[2,1-biquinazoline-6,12-dione antibacterial compounds and methods
  申请人：PathoGenesis Corporation

  公开号：US05441955A1

  公开（公告）日：1995-08-15

  Methods, compounds and compositions are provided form inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic mycobacterial infections in vivo using indolo[2,1-b]quinazoline-6,12-dione compounds of the formula (I): ##STR1## wherein A, B, C, D, E, F, G and H are independently selected from carbon and nitrogen, or A and B or C and D can be taken together to be nitrogen or sulfur, and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis, and may be used alone, or in combination with other anti-Mycobacterium tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, rifabutin, streptomycin and ciprofloxacin, to provide new agents for the treatment of tuberculosis, including multidrug-resistant tuberculosis (MDRTB).

  提供了一种用于体外抑制病原性分枝杆菌生长和用于体内治疗病原性分枝杆菌感染的方法、化合物和组合物，使用式(I)的吲哚并[2,1-b]喹唑啉-6,12-二酮化合物：##STR1## 其中A、B、C、D、E、F、G和H独立地选自碳和氮，或A和B或C和D可以结合在一起成为氮或硫，并且其药学上可接受的盐。这些方法、化合物和组合物特别适用于抑制结核分枝杆菌的生长，并可单独使用，或与其他抗结核分枝杆菌药物（如异烟肼、利福平、吡嗪酰胺、利福布汀、链霉素和环丙沙星）结合使用，以提供用于治疗结核病的新药物，包括多药耐药结核病（MDRTB）。
• Direct Catalytic Asymmetric Synthesis of β-Hydroxy Acids from Malonic Acid
  作者：Hang Gao、Zhenli Luo、Pingjin Ge、Junqian He、Feng Zhou、Peipei Zheng、Jun Jiang

  DOI：10.1021/acs.orglett.5b02891

  日期：2015.12.18

  A nickel(II) catalyzed asymmetric synthesis of β-hydroxy acids from malonic acid and ketones was developed, revealing for the first time the synthetic utility of malonic acid in the construction of chiral carboxyl acids; importantly, the synthetic potential of this strategy was further demonstrated by the rapid construction of cephalanthrin A, phaitanthrin B, cruciferane, and rice metabolites.

  开发了镍（II）催化由丙二酸和酮不对称合成β-羟基酸的方法，这首次揭示了丙二酸在手性羧酸的合成中的合成作用。重要的是，该方法的合成潜力通过快速构建头孢菌素A，紫杉醇B，十字花青素和大米代谢产物得到了进一步证明。
• Ni(II)-Catalyzed Enantioselective Synthesis of β-Hydroxy Esters with Carboxylate Assistance
  作者：Na Wang、Hongxin Liu、Hang Gao、Jiafeng Zhou、Longzhangdi Zheng、Juan Li、Hong-Ping Xiao、Xinhua Li、Jun Jiang

  DOI：10.1021/acs.orglett.9b02297

  日期：2019.9.6

  decarboxylative aldol reaction between malonic acid half-oxyesters and various carbonyls with carboxylate assistance was developed, affording structurally diverse β-hydroxy esters with good yields and enantioselectivities under mild conditions. Importantly, the broad substrate scope of this methodology enabled rapid accesses to several natural products and their analogues as exemplified by phenylpropanoid, phaitanthrin

  建立了Ni-恶唑啉配合物催化丙二酸半含氧酸酯和各种羰基在羧酸酯辅助下的不对称脱羧醛醇缩合反应，在温和条件下以良好的收率和对映选择性提供了结构多样的β-羟基酯。重要的是，这种方法的广泛的底物范围使人们能够快速获得几种天然产物及其类似物，例如苯丙烷，类赤霉素B和邻苯二甲酸酯。
• Synthesis of 6-Alkynyl-6-hydroxyindoloquinazolinone Scaffolds via Copper-Catalyzed Alkynylation of Tryptanthrins
  作者：Yu Guo、Ebrahim-Alkhalil M. A. Ahmed、De-Kun Ma、Jun Jiang、Hongxin Liu、Xinhua Li、Juan Li、Hong-Ping Xiao

  DOI：10.1055/a-1533-1080

  日期：2021.9

  alkynes under mild reaction conditions. The developed method provides an array of synthetic building blocks of 6-alkynyl-6-hydroxyindoloquinazolinone compounds in moderate to good yields with varied functional group compatibility. Furthermore, the obtained adducts can be smoothly converted into versatile building blocks via hydrogenation, hydration, and further Sonogashira coupling transformations.

  我们报道了在温和的反应条件下，铜催化的色氨酸与末端炔烃的直接炔化反应。所开发的方法以中等至良好的产率提供了一系列 6-炔基-6-羟基吲哚并喹唑啉酮化合物的合成结构单元，具有不同的官能团兼容性。此外，所获得的加合物可以通过氢化、水合和进一步的 Sonogashira 偶联转化顺利转化为通用结构单元。
• β-Cyclodextrin catalysed synthesis of tryptanthrin in water
  作者：Atul Kumar、Vishwa Deepak Tripathi、Promod Kumar

  DOI：10.1039/c0gc00523a

  日期：——

  An efficient and green method has been developed for the synthesis of tryptanthrin employing β-cyclodextrin as a catalyst in aqueous media at room temperature from isatoic anhydride and isatin. The reactions were performed under mild conditions to afford biologically active natural product tryptanthrin in excellent yields.

  一种高效且环保的方法已被开发，用于在室温下利用β-环糊精作为催化剂，在水相中从异烟酸酐和异靛中合成色氨酸黄酮。反应在温和的条件下进行，能够以优异的产率获得具有生物活性的天然产物色氨酸黄酮。