8-(羟基甲基)-6,11-二甲基-4H-[1,3]恶唑并[5,4,3-ij]吡啶并[3,2-g]喹啉-4,10(11H)-二酮 | 30408-30-1

• 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
• 中文名称: 8-(羟基甲基)-6,11-二甲基-4H-[1,3]恶唑并[5,4,3-ij]吡啶并[3,2-g]喹啉-4,10(11H)-二酮
• 中文别名: 尼博霉素
• 英文名称: nybomycin
• 英文别名: 8-hydroxymethyl-6,11-dimethyl-11H-oxazolo[5,4,3-ij]pyrido[3,2-g]quinoline-4,10-dione；8-Hydroxymethyl-6,11-dimethyl-11H-oxazolo[5,4,3-ij]pyrido[3,2-g]chinolin-4,10-dion；(Nybomycin)；6-(hydroxymethyl)-3,10-dimethyl-15-oxa-3,13-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(16),2(7),5,8,10-pentaene-4,12-dione
• CAS: 30408-30-1
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: HKMUGCUFXWTNSP-UHFFFAOYSA-N

物化性质

• 熔点：
  325-330°
• 沸点：
  538.7±50.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)
• 溶解度：
  加热条件下溶于乙酸 (80%)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  己基-5-壬基氯 、 8-(羟基甲基)-6,11-二甲基-4H-[1,3]恶唑并[5,4,3-ij]吡啶并[3,2-g]喹啉-4,10(11H)-二酮 在 吡啶 作用下， 反应 24.0h， 以36%的产率得到nybomycin 5-hexynoyl ester
  参考文献：
  名称：

  Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp.

  摘要：

  In the course of our search for anti-dormant Mycobacterial substances, nybomycin ( 1) was re-discovered from the culture broth of a marine-derived Streptomyces sp. on the bioassay-guided separation. Compound 1 showed anti-microbial activity against Mycobacterium smegmatis and Mycobacterium bovis BCG with the MIC of 1.0 mu g/mL under both actively growing aerobic conditions and dormancy inducing hypoxic conditions. Compound 1 is also effective to Mycobacterium tuberculosis including the clinically isolated strains. The mechanistic analysis indicated that 1 bound to DNA and induces a unique morphological change to mycobacterial bacilli leading the bacterial cell death. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.033
• 作为产物：
  描述：

  nybomycin acetate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 8-(羟基甲基)-6,11-二甲基-4H-[1,3]恶唑并[5,4,3-ij]吡啶并[3,2-g]喹啉-4,10(11H)-二酮
  参考文献：
  名称：

  尼霉素。七。制备至霉素和脱氧霉素的途径。

  摘要：

  DOI：

  10.1021/ja00796a037

文献信息

• [EN] COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES<br/>[FR] COMPOSÉS ET SUBSTRATS ANTITUMORAUX NQO1
  申请人：UNIV ILLINOIS

  公开号：WO2013056073A1

  公开（公告）日：2013-04-18

  Compounds of Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compounds are useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.

  化合物的化学式（I）可以选择性地对多种不同类型的癌细胞具有致命作用。这些化合物对于管理、治疗、控制或辅助治疗疾病非常有用，其中选择性的致命作用在化疗疗法中具有益处。
• [EN] ANTIBIOTICS EFFECTIVE FOR GRAM-NEGATIVE PATHOGENS<br/>[FR] ANTIBIOTIQUES EFFICACES CONTRE LES PATHOGÈNES GRAM-NÉGATIFS
  申请人：UNIV ILLINOIS

  公开号：WO2019177975A1

  公开（公告）日：2019-09-19

  Disclosed herein are antibacterial compounds that accumulate in Gram-negative bacteria, methods of preparing the compounds, and methods of using the compounds to inhibit or kill microbes, and methods of treating microbial infections, such as Gram-negative bacterial infections. Compounds selected for conversion to potential Gram-negative antibacterial compounds were identified based on compounds having low globularity and low flexibility. Amine substituents were then strategically added to the selected compounds to provide compounds having antibacterial activity against Gram-negative bacteria.

  本文披露了在革兰氏阴性细菌中积累的抗菌化合物，制备这些化合物的方法，以及利用这些化合物抑制或杀灭微生物，以及治疗微生物感染的方法，如革兰氏阴性细菌感染。选择用于转化为潜在革兰氏阴性抗菌化合物的化合物是基于具有低球形度和低柔性的化合物。然后在所选的化合物中策略性地添加氨基取代基，以提供对革兰氏阴性细菌具有抗菌活性的化合物。
• [EN] TOPOISOMERASE INHIBITORS WITH ANTIBACTERIAL AND ANTCANCER ACTIVITY<br/>[FR] INHIBITEURS DE LA TOPOISOMÉRASE AYANT UNE ACTIVITÉ ANTIBACTÉRIENNE ET UNE ACTIVITÉ ANTI-CANCÉREUSE
  申请人：UNIV ILLINOIS

  公开号：WO2018237140A1

  公开（公告）日：2018-12-27

  Inhibitors of human topoisomerase II (Top2) are the backbone of numerous cancer chemotherapy regimens. Unfortunately, the onset of toxicity severely limits the utility of these powerful drugs. There is some conservation between human Top2 and bacterial homologues (DNA gyrase and TopoIV). Thus, the conversion of antibacterial topoisomerase inhibitors into antineoplastic agents is an intriguing strategy for anticancer compounds. Herein is described the conversion of deoxynybomycin (DNM), a natural product and DNA gyrase inhibitor with minimal cytotoxicity, into a compound that has anticancer activity. Detailed in vitro and cell culture experiments demonstrate that these compounds inhibit Top2 and also act upon topoisomerase I. Similar approaches are applicable to other classes of gyrase inhibitors and other antibacterial targets for discovery of new anticancer drugs.

  人类拓扑异构酶II（Top2）的抑制剂是许多癌症化疗方案的基础。不幸的是，毒性的发生严重限制了这些强效药物的实用性。人类Top2和细菌同源物（DNA旋转酶和TopoIV）之间存在一定的保守性。因此，将抗菌拓扑异构酶抑制剂转化为抗肿瘤药物是一种有趣的抗癌化合物策略。本文描述了将脱氧尼伯霉素（DNM），一种天然产物和DNA旋转酶抑制剂，转化为具有抗癌活性的化合物。详细的体外和细胞培养实验证明这些化合物抑制Top2，同时也对拓扑异构酶I起作用。类似的方法适用于其他类别的旋转酶抑制剂和其他抗菌靶标，用于发现新的抗癌药物。
• ANTIBACTERIAL AGENT
  申请人：JUNTENDO EDUCATIONAL FOUNDATION

  公开号：US20150322033A1

  公开（公告）日：2015-11-12

  An antibacterial agent comprising a compound represented by the following general formula (I), which can exhibit potent antibacterial activity against bacteria that have acquired resistance to quinolones (in the formula, R 1 and R 4 represents hydrogen atom, hydroxyl group, or a lower alkoxy group; R 2 and R 3 represents hydrogen atom or hydroxyl group; W represents hydrogen atom, a lower cyclic alkyl group, or a lower alkoxy group; R 1′ and R 5′ represents hydrogen atom; R 2′ and R 3′ represents hydrogen atom, hydroxyl group, or a lower alkoxy group; and R 4′ represents hydrogen atom or hydroxyl group).

  一种抗菌剂，包括以下一般式（I）所代表的化合物，该化合物可以对已经对喹诺酮产生抗药性的细菌表现出强效的抗菌活性（在该式中，R1和R4代表氢原子、羟基或较低的烷氧基；R2和R3代表氢原子或羟基；W代表氢原子、较低的环烷基或较低的烷氧基；R1'和R5'代表氢原子；R2'和R3'代表氢原子、羟基或较低的烷氧基；R4'代表氢原子或羟基）。
• [EN] SMALL-MOLECULES ACTIVE AGAINST GRAM-NEGATIVE BACTERIA<br/>[FR] PETITES MOLÉCULES ACTIVES CONTRE LES BACTÉRIES À GRAM NÉGATIF
  申请人：UNIV ILLINOIS

  公开号：WO2017156519A1

  公开（公告）日：2017-09-14

  Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

  本发明涉及新型化合物，这些化合物在革兰氏阴性细菌中积累。本发明还涉及使用这些化合物进行抗微生物治疗的方法。