3,5-dibromoisobenzofuran-1(3H)-one | 102126-70-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3,5-dibromoisobenzofuran-1(3H)-one
• 英文别名: 3,5-Dibromo-3H-isobenzofuran-1-one；3,5-dibromo-3H-2-benzofuran-1-one
• CAS: 102126-70-5
• 化学式: C₈H₄Br₂O₂
• 分子量: 291.927
• InChiKey: AVHYDEJTOWNHJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-dibromoisobenzofuran-1(3H)-one 在 一水合肼 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 3.5h， 生成 6-溴-1-氯-二氮杂萘
  参考文献：
  名称：

  Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery

  摘要：

  Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases, Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzypoxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

  DOI：

  10.1021/acs.jmedchem.5b00515
• 作为产物：
  描述：

  4-溴-2-甲基苯甲酸 在 sodium persulfate 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 四丁基溴化铵 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 22.0h， 生成 3,5-dibromoisobenzofuran-1(3H)-one
  参考文献：
  名称：

  镍催化立体收敛交叉偶联反应对映选择性合成 3-芳基苯酞

  摘要：

  外消旋 3-溴代苯酞和芳基硼酸的镍催化不对称 Suzuki-Miyaura 交叉偶联可用于以中等至优异的反应产率合成多种手性 3-芳基苯酞。反应以立体收敛的方式进行，并且对于大多数检查的实施例都观察到了高对映选择性。许多官能团如醛、酯和溴化物具有良好的耐受性。杂芳族硼酸也是该反应中的有效偶联伙伴。

  DOI：

  10.1039/d1ob00487e

文献信息

• Nickel-catalyzed reductive defunctionalization of esters in the absence of an external reductant: activation of C–O bonds
  作者：Yasuaki Iyori、Kenjiro Takahashi、Ken Yamazaki、Yusuke Ano、Naoto Chatani

  DOI：10.1039/c9cc07710c

  日期：——

  The nickel-catalyzed reductive cleavage of esters in the absence of an external reductant, which involves the cleavage of an inert acyl C–O bond in O-alkyl esters is reported.

  镍催化剂在无外部还原剂的情况下，报告了酯的还原裂解，其中涉及对惰性酰基C-O键进行裂解，这种裂解发生在O-烷基酯中。
• Design, Synthesis, and Structure–Activity Relationship Study of Potent MAPK11 Inhibitors
  作者：Mengdie Gong、Mingyan Tu、Hongxia Sun、Lu Li、Lili Zhu、Honglin Li、Zhenjiang Zhao、Shiliang Li

  DOI：10.3390/molecules27010203

  日期：——

  there are no approved drugs for HD on the market. Studies have found that MAPK11 can serve as a potential therapeutic target for HD. Regrettably, no MAPK11 small molecule inhibitors have been approved at present. This paper presents three series of compounds that were designed and synthesized based on the structure of skepinone-L, a known MAPK14 inhibitor. Among the synthesized compounds, 13a and 13b,

  亨廷顿病（HD）是一种罕见的单基因神经退行性疾病，只能对症治疗。目前，市场上还没有批准用于 HD 的药物。研究发现，MAPK11 可以作为 HD 的潜在治疗靶点。遗憾的是，目前尚未批准任何 MAPK11 小分子抑制剂。本文介绍了基于已知 MAPK14 抑制剂 skepinone-L 的结构设计和合成的三个系列化合物。在合成的化合物中，13a和13b，IC 50值分别为 6.40 nM 和 4.20 nM，显示出对 MAPK11 的最佳抑制活性。此外，还详细讨论了构效关系 (SAR)，这对于优化 MAPK11 抑制剂以获得更好的抗 HD 活性和效果具有建设性。
• PROTOZOAN PARASITE GROWTH INHIBITORS
  申请人：Northeastern University

  公开号：US20150259331A1

  公开（公告）日：2015-09-17

  Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be used to inhibit growth of protozoan parasites such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Plasmodium spp.

  用于抑制原生动物寄生虫生长的化合物和方法。通过向主体施用如本文所述的治疗有效量的化合物来治疗原生动物寄生虫感染的方法。这些化合物和方法可用于抑制如非洲锥虫、克鲁兹锥虫、利什曼原虫属和疟原虫属等原生动物寄生虫的生长。
• Furan ring opening - isocoumarine ring closure: A recyclization reaction of 2-carboxyaryldifurylmethanes
  作者：Vladimir T. Abaev、Artem S. Dmitriev、Sergey A. Podelyakin、Alexander V. Butin、Andrey V. Gutnov

  DOI：10.1002/jhet.5570430510

  日期：2006.9

  A general method for the synthesis of isocoumarine derivatives has been developed. Bis(5-R-2-furyl)methylbenzoic acids (R = methyl, ethyl) underwent recyclization and subsequent cyclization into tetracyclic isochromene-1-one derivatives under treatment with hydrogen chloride in methanol. It has been shown that intermediate 4-(5-R-furan-2-yl)-3-(3-oxo-3-R-propyl)-isochromene-1-ones can be obtained selectively

  已经开发了合成异香豆素衍生物的通用方法。将双（5-R-2-呋喃基）甲基苯甲酸（R =甲基，乙基）进行环化，然后在甲醇中用氯化氢处理，将其环化为四环异色烯-1-酮衍生物。已经表明，通过改变氢的浓度，可以选择性地获得中间体4-（5-R-呋喃-2-基）-3-（3-氧代-3-R-丙基）-异亚甲基-1-酮。氯化物和反应时间。在R ＝叔丁基的情况下，无论反应如何，仅分离出相应的4- [5-（叔丁基）-2-呋喃基] -3-（4,4-二甲基-3-氧戊基）-1-异壬酮。情况。
• Facile construction of pyrrolo[1,2-b]isoquinolin-10(5H)-ones via a redox-amination–aromatization–Friedel–Crafts acylation cascade reaction and discovery of novel topoisomerase inhibitors
  作者：Shanchao Wu、Na Liu、Guoqiang Dong、Lin Ma、Shengzheng Wang、Wencai Shi、Kun Fang、Shuqiang Chen、Jian Li、Wannian Zhang、Chunquan Sheng、Wei Wang

  DOI：10.1039/c6cc03071h

  日期：——

  An efficient redox-amination-aromatization-Friedel-Crafts acylation cascade process from trans-4-hydroxyproline and 2-formylbenzoic acids has been developed for the synthesis of pyrrolo[1,2-b]isoquinolin-10(5H)-ones. Compound 3h was identified as a new potent dual topoisomerase I/II inhibitor.

  从反式-4-羟基脯氨酸和2-甲酰基苯甲酸开发了一种有效的氧化还原胺化芳构化Friedel-Crafts酰化级联方法，用于合成吡咯并[1,2-b]异喹啉-10（5H）-。化合物3h被鉴定为新型强效双重拓扑异构酶I / II抑制剂。