5-fluoro-1-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 5-fluoro-1-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione
• 英文别名: 5-fluoro-1-methyl-3,1-benzoxazine-2,4(1H)-dione；5-Fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione；5-fluoro-1-methyl-3,1-benzoxazine-2,4-dione
• 化学式: C₉H₆FNO₃
• 分子量: 195.15
• InChiKey: AKHVJQPMVFVKLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-fluoro-1-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 13.5h， 生成 8-fluoro-9-hydroxy-4-methyl-2,4-dihydro-1H-pyrrolo[3,4-b]quinoline-1,9(4H)-dione
  参考文献：
  名称：

  使用pKa引导的碱促进的环戊醇与环戊酸酐的合成环状N取代的4-喹啉酮：Penicinotam的总合成。

  摘要：

  开发了一种使用等位酸酐和多种可烯化伙伴的阴离子环化策略，以提供80多种新型的环稠合N取代的4-喹啉酮，这是一种代表性不足的特权模板。确定了控制转化效率的多种因素，从而形成了可靠且可调谐的合成平台，适用于具有多种去质子化敏感性的多种底物，例如四甲酸和四氢代酸，环状1,3-二酮和环烷酮。应用于生物活性的吡咯烷嗪融合的4-喹啉酮青霉素3的合成中，生物碱的合成过程最简单，最高，分三步进行，总产率为36％。

  DOI：

  10.1021/acs.joc.9b02541
• 作为产物：
  描述：

  2-氨基-6-氟苯甲酸 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 5-fluoro-1-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione
  参考文献：
  名称：

  吴茱萸碱衍生物作为有效杀虫剂候选物的发现

  摘要：

  在寻找新型更有效的杀虫剂时，天然产物具有良好的环境相容性、多种生物活性、独特的支架和作用方式，可作为理想的模板化合物。我们发现吴茱萸果实的主要活性成分天然产物吴茱萸碱对鳞翅目具有明显的杀虫活性。害虫。为了继续我们的研究，我们合理设计和合成了一系列吴茱萸碱衍生物3a-3aa。杀幼虫活性结果表明，大部分目标化合物对Mythimna separata、Plutella xylostella和Helicoverpa armigera的效果优于吴茱萸碱、苦参碱和鱼藤酮，其中3z表现出优异的杀幼虫活性（2.5 mg/L对M. separata的杀幼虫活性为65%， 75% 1.0 mg/L 对P. xylostella和 85% 10 mg/L 对H. armigera，分别），远优于吴茱萸碱（0%）、苦参碱（0%）和鱼藤酮（0%）。初步构效关系表明吴茱萸碱E环上的氟原子对杀幼虫活性有正向影响。钙显像

  DOI：

  10.1016/j.bmc.2022.116727

文献信息

• [EN] 3-ACYL-INGENOLS II<br/>[FR] 3-ACYL-INGÉNOLS II
  申请人：LEO PHARMA AS

  公开号：WO2012083954A1

  公开（公告）日：2012-06-28

  The invention relates to compounds of general formula I, (I), wherein R is wherein R is aryl substituted by R3; or R is (C3-Ci3)-cycloalkyl, (C3-Ci3)- cycloalkenyl or (C7-Ci3)-cycloalkynyl optionally substituted by R4; and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use -alone or in combination with one or more other pharmaceutically active compounds- in therapy, for preventing, treating or ameliorating diseases or conditions responsive to stimulation of neutrophil oxidative burst, responsive to stimulation of keratinocyte IL-8 release or responsive to induction of necrosis.

  该发明涉及一般式I的化合物，其中R是芳基，被R3取代；或者R是(C3-C13)-环烷基，(C3-C13)-环烯基或(C7-C13)-环炔基，可选择性地被R4取代；以及其在治疗中的药用盐、水合物或溶剂化合物，可单独使用或与一个或多个其他药用活性化合物结合使用，用于预防、治疗或改善对中性粒细胞氧化爆发刺激敏感的疾病或症状，对角质细胞IL-8释放刺激敏感的疾病或症状，或对坏死诱导敏感的疾病或症状。
• Novel Evodiamine-Based Sulfonamide Derivatives as Potent Insecticide Candidates Targeting Insect Ryanodine Receptors
  作者：Jingbo Liu、Bingyan Guo、Siying Zhong、Yabing Shi、Zhengping Li、Zhenwu Yu、Zesheng Hao、Li Zhang、Fengyun Li、Yuanhong Wang、Yuxin Li

  DOI：10.1021/acs.jafc.3c05680

  日期：2024.1.17

  global food security. On the basis of our prior research focused on identifying insecticidal leads targeting insect ryanodine receptors (RyRs), we aimed to identify evodiamine scaffold-based novel insecticides. Thus, a variety of evodiamine-based derivatives were designed, synthesized, and assessed for their insecticidal activity against the larvae of Mythimna separata (M. separata) and Plutella xylostella

  害虫是高效农业生产的重要障碍，并对全球粮食安全构成威胁。在我们之前专注于识别针对昆虫兰尼碱受体（RyRs）的杀虫先导化合物的研究基础上，我们的目标是识别基于吴茱萸碱支架的新型杀虫剂。因此，设计、合成了多种基于吴茱萸碱的衍生物，并评估了它们对粘虫（ M. separata ）和小菜蛾（ P. xylostella ）幼虫的杀虫活性。初步生物测定结果表明，与吴茱萸碱、苦参碱和鱼藤酮相比，超过一半的目标化合物对M. separata表现出优异的活性。其中，化合物21m显示出最有效的杀幼虫效率，在2.5 mg/L时死亡率高达93.3%，比吴茱萸碱（10 mg/L时为10.0%）、苦参碱（200 mg/L时为10.0%）有显着改善。 ）和鱼藤酮（200 mg/L 时为 30.0%）。对于小菜蛾，化合物21m和21o显示出较高的杀幼虫活性，其LC 50值分别为9.37 × 10 –2和0.13 mg/L，超过了吴茱萸碱（13
• Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders:  Structure−Activity Relationship
  作者：Stig Jönsson、Gunnar Andersson、Tomas Fex、Tomas Fristedt、Gunnar Hedlund、Karl Jansson、Lisbeth Abramo、Ingela Fritzson、Olga Pekarski、Anna Runström、Helena Sandin、Ingela Thuvesson、Anders Björk

  DOI：10.1021/jm031044w

  日期：2004.4.1

  Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).
• Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment of actinic keratosis and non-melanoma skin cancer
  作者：Gunnar Grue-Sørensen、Xifu Liang、Kristoffer Månsson、Per Vedsø、Morten Dahl Sørensen、Anke Soor、Martin Stahlhut、Malene Bertelsen、Karen Margrethe Engell、Thomas Högberg

  DOI：10.1016/j.bmcl.2013.11.073

  日期：2014.1

  Ingenol 3-benzoates were investigated with respect to chemical stability, pro-inflammatory effects, cell death induction and PKC delta activation. A correlation between structure, chemical stability and biological activity was found and compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of actinic keratosis. We also provided further support for involvement of PKC delta for induction of oxidative burst and cytokine release. Molecular modeling and dynamics calculations corroborated the essential interactions between key compounds and C1 domain of PKC delta. (C) 2013 Elsevier Ltd. All rights reserved.
• New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations
  作者：Guoqiang Dong、Shengzheng Wang、Zhenyuan Miao、Jianzhong Yao、Yongqiang Zhang、Zizhao Guo、Wannian Zhang、Chunquan Sheng

  DOI：10.1021/jm300605m

  日期：2012.9.13

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.