9-chloroindolo[2,1-b]quinoxazoline-6,12-dione | 77603-39-5

• 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: 9-chloroindolo[2,1-b]quinoxazoline-6,12-dione
• 英文别名: 9-chloroindolo[2,1-b]quinazoline-6,12-dione
• CAS: 77603-39-5
• 化学式: C₁₅H₇ClN₂O₂
• 分子量: 282.686
• InChiKey: KHONZILMMZKIQL-UHFFFAOYSA-N

物化性质

• 沸点：
  513.4±52.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

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：

  9-chloroindolo[2,1-b]quinoxazoline-6,12-dione 在 盐酸 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 为溶剂， 反应 74.5h， 生成 9-Piperazin-1-ylindolo[2,1-b]quinazoline-6,12-dione;hydrochloride
  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：

  Ν-(3-chlorophenyl)-2-hydroxyiminoacetamide 在 硫酸 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.33h， 生成 9-chloroindolo[2,1-b]quinoxazoline-6,12-dione
  参考文献：
  名称：

  通过芳基卤化物和胺类化合物作为抗肿瘤药和抗-MRSA试剂合成取代的色胺酮

  摘要：

  发现天然生物碱类胰蛋白酶（吲哚[2,1-b]喹唑啉-6,12-二酮）及其类似物表现出有效的抗肿瘤和抗-MRSA活性。已经开发了一种有效且方便的方法，该方法通过使取代的色胺酮与仲胺反应以中等至良好的产率合成色胺酮D-环衍生物。一些新化合物对人肿瘤细胞系A549，HCT116和MDA-MB-231表现出抗肿瘤活性，低微摩尔水平的平均IC 50值。此外，某些化合物显示出优异的抗MRSA活性，并且比万古霉素更有效，Mu50，RN4220和Newman菌株的MIC值为0.31–1.25μg/ mL。

  DOI：

  10.1016/j.tet.2019.05.030

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。
• 一锅串联反应合成色胺酮类生物碱的方法
  申请人：河南师范大学

  公开号：CN106831784B

  公开（公告）日：2019-07-19

  本发明公开了一种串联反应合成色胺酮类生物碱的方法，属于有机合成技术领域。本发明的技术方案要点为：（1）将邻溴苯乙酮类化合物、二甲基亚砜和碘单质置于反应容器中，于110℃加热搅拌反应；（2）冷却至室温，加入邻氨基苯甲酰胺类化合物、铜盐和碱，于室温搅拌反应，之后升温至100℃搅拌反应至TLC跟踪监测反应完全，最终制得色胺酮类生物碱。本发明克服了目前该类化合物合成方法中原料种类少、底物适用范围窄、反应条件苛刻、使用对水敏感的强酸性试剂等缺点，是一种一锅串联合成色胺酮类生物碱的高效方法，该合成方法具有起始原料简单易得、反应条件温和和操作简单等优点。