2-Anilino-6-fluoro-4-oxochromene-3-carbaldehyde | 1168003-68-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-Anilino-6-fluoro-4-oxochromene-3-carbaldehyde
• 英文别名: 2-anilino-6-fluoro-4-oxochromene-3-carbaldehyde
• CAS: 1168003-68-6
• 化学式: C₁₆H₁₀FNO₃
• 分子量: 283.259
• InChiKey: FXHRCJVWTVSKPR-UHFFFAOYSA-N

物化性质

• 沸点：
  412.7±45.0 °C(predicted)
• 密度：
  1.500±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Anilino-6-fluoro-4-oxochromene-3-carbaldehyde 在 硫代苯甲酰胺 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 以76%的产率得到6-fluoro-4-oxo-4H-chromene-3-carbothioic acid N-phenylamide
  参考文献：
  名称：

  Mechanism of unusual formation of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides and their antimicrobial evaluation

  摘要：

  6/6,7-Substituted 3-formylchromones (9a-e) react with 2 equivalents of 2-phenyl-4-dimethylamino-1-thia-3-azabuta-1,3-diene (10) or thiobenzamide (11) in refluxing toluene to furnish novel substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (12a-e). However, reactions of substituted 2-anilino-3-formylchromones (15a-d) with thiobenzamide (11, 2 equivalents) in refluxing xylene furnish 4-oxo-4H-chromene-3-carbothioic acid N-phenylamide (17a-d) in high yields. A mechanistic rationalization of the conversion of 2-anilino-3-formylchromones (15a-d) to N-phenylamides (17a-d), and 3-formylchromones (9a-e) to the corresponding thioaldehydes, is proffered. All the compounds (12a-e, 17a-d) display very high antifungal and antibacterial activities against a number of strains. Dithiazole 12d exhibits a very high antifungal activity (MIC 5 mu g/ml) against Geotrichum candidum, better than fluconazole (MIC 09 mu g/ml) and also possesses good antibacterial activity (MIC 52 mu g/ml) against Shigella flexneri. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.03.030
• 作为产物：
  描述：

  4-氟苯基醋酸酯 在 aluminum (III) chloride 、 溶剂黄146 、 三氯氧磷 作用下， 以 苯 为溶剂， 生成 2-Anilino-6-fluoro-4-oxochromene-3-carbaldehyde
  参考文献：
  名称：

  3-Formylchromone based topoisomerase IIα inhibitors: discovery of potent leads

  摘要：

  取代的3-甲醛吡喃酮被合成并评价为人类DNA拓扑异构酶IIα（hTopo-IIα）酶的抑制剂。脱连环、松弛和DNA嵌插实验的结果显示，这些化合物（11b、12a、12b、12d、12e、13a和13b）对hTopo-IIα酶显示出强大的抑制活性，并且是非嵌插剂。这些化合物还表现出显著的体外细胞毒性（LC50范围为0.5至8.6 μM），对前列腺（PC-3）癌细胞系的毒性可与标准药物依托泊苷相比。为了进一步探究3-甲醛吡喃酮衍生物的可能作用机制，还进行了分子对接研究，结果显示，所研究的化合物很好地适应hTopo-IIα酶的ATP结合口袋，具有良好的对接分数，并与催化位点的关键残基形成非键相互作用。

  DOI：

  10.1039/c3md00125c

文献信息

• Reduction of chromano–piperidine-fused isoxazolidines: Tandem intramolecular rearrangements leading to 2-(methylamino)-4-oxo- N -phenyl- N -propyl-4 H -chromene-3-carboxamide
  作者：Gagandeep Singh、Naman Gupta、Vivek Gupta、Mohan Paul Singh Ishar

  DOI：10.1016/j.tetlet.2017.05.032

  日期：2017.6

  Reductive ring opening of isoxazolidine moiety of chromano–piperidine-fused isoxazolidines (3a–c) with HCOONH4 and 10% Pd/C in a mixture of solvents (THF/MeOH) at ambient temperature, affords novel 2-(methylamino)-4-oxo-N-phenyl-N-propyl-4H-chromene-3-carboxamide (4), which is apparently derived from reductive NO bond cleavage followed by tandem intramolecular rearrangements. Plausible mechanistic

  在环境温度下，用HCOONH 4和10％Pd / C在色氨酸-哌啶稠合的异恶唑烷（3a – c）中的异恶唑烷部分进行还原性开环，得到新颖的2-（甲基氨基）-4氧代ñ苯基ñ -丙基-4- ħ色烯-3-甲酰胺（4），其显然是从还原性N-衍生O键裂解，随后通过串联的分子内重排。提出了形成化合物4的合理的机械原理。
• Domino routes to substituted benzoindolizines: tandem reorganization of 1,3-dipolar cycloadducts of nitrones with allenic esters/ketones and alternative cycloaddition–palladium catalyzed cyclization pathway
  作者：Ashish Kapur、Kamal Kumar、Lakhwinder Singh、Parminder Singh、Munusamy Elango、Venkatesan Subramanian、Vivek Gupta、Priyanka Kanwal、Mohan Paul S. Ishar

  DOI：10.1016/j.tet.2009.03.076

  日期：2009.6

  intramolecular aza Diels–Alder reaction in the intermediate C. DFT calculations of various parameters for diene and dienophile components in the proposed intermediate C have revealed that conformational constraints imposed by the alkyl groups (R=Me, Et) favor intramolecular aza-Diels–Alder cycloaddition. An alternative domino route to benzoindolizines (9a,d,g) involving sequential one-pot cycloaddition of azadienes

  的反应Ç - （4-氧代-4- ħ [1]苯并吡喃-3-基） - ñ -苯基硝酮（7）与丙二烯酯（8A - C ^）和丙二烯酮类（18A - d）配料benzoindolizines（9A - ķ，19a – d），收益率很高。假定苯并吲哚并嗪的形成涉及将烯丙基酯/酮的C2-C3π键上的1,3-偶极区域选择性加成，然后环加合物进行多米诺转化，这涉及中间体C中的分子内氮杂Diels-Alder反应。对拟议的中间体C中二烯和亲二烯体组分的各种参数的计算表明，烷基（R = Me，Et）施加的构象约束有利于分子内氮杂-Diels-Alder环加成反应。苯并吲哚并嗪（9a，d，g）的另一种多米诺途径涉及将氮杂二烯（22a – c）与甲硅烷基烯醇醚（23）相继进行一锅环加成反应），然后进行钯（0）催化的Heck偶联反应。这两种方法都代表了合成苯并吲哚并嗪的新颖多米诺路线。
• Cytotoxic activity of 3-(5-phenyl-3 H -[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4 H -chromene-3-carbothioic acid N -phenylamides
  作者：Tilak Raj、Richa Kaur Bhatia、Ashish kapur、Madhunika Sharma、A.K. Saxena、M.P.S. Ishar

  DOI：10.1016/j.ejmech.2009.11.001

  日期：2010.2

  6/6,7-Substituted-3-formylchromones (8a-g) were reacted with 2 equivalents thiobenzamide (9) in refluxing toluene to furnish substituted -3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (10a-g) in high yields. Similarly, when substituted-2-anilino-3-formylchromones (8a-d) were reacted with thiobenzamide (9, 2 equivalents) in refluxing xylene, 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides (11a-d) were obtained in high yields. All the compounds (10a-g) and (11a-d) display significant cytotoxic activity against a number of human cancer cell lines. Among these compounds 10e (IC50 = 10 mu M), 10b (IC50 = 14.6 mu M) and 10a (IC50 = 10.5 mu M) showed maximum cytotoxic activity on neuroblastoma. Also, the compound 10c (IC50 = 10.5 mu M) showed maximum cytotoxic activity on ovarian cancer cell line. (C) 2009 Elsevier Masson SAS. All rights reserved.
• 3-Formylchromone based topoisomerase IIα inhibitors: discovery of potent leads
  作者：Satyajit Singh、Ashish Triambak Baviskar、Vaibhav Jain、Nidhi Mishra、Uttam Chand Banerjee、Prasad V. Bharatam、Kulbhushan Tikoo、Mohan Paul Singh Ishar

  DOI：10.1039/c3md00125c

  日期：——

  Substituted 3-formylchromones were synthesized and evaluated as inhibitors of the human DNA topoisomerase IIα (hTopo-IIα) enzyme. The results of the decatenation, relaxation and DNA intercalation assays revealed that the compounds (11b, 12a, 12b, 12d, 12e, 13a and 13b) exhibited potent inhibitory activity against the hTopo-IIα enzyme, and are nonintercalating agents. These compounds also possess significant in vitro cytotoxicity (LC50 ranges from 0.5–8.6 μM) against prostate (PC-3) cancerous cell line as seen in comparison to the standard drug etoposide. To further probe the plausible mode of action of 3-formylchromone derivatives, molecular docking studies have also been carried out, which showed that the compounds under investigation fitted well in the ATP binding pocket of hTopo-IIα enzyme with good docking scores and form nonbonding interactions with the crucial residues of the catalytic site.

  取代的3-甲醛吡喃酮被合成并评价为人类DNA拓扑异构酶IIα（hTopo-IIα）酶的抑制剂。脱连环、松弛和DNA嵌插实验的结果显示，这些化合物（11b、12a、12b、12d、12e、13a和13b）对hTopo-IIα酶显示出强大的抑制活性，并且是非嵌插剂。这些化合物还表现出显著的体外细胞毒性（LC50范围为0.5至8.6 μM），对前列腺（PC-3）癌细胞系的毒性可与标准药物依托泊苷相比。为了进一步探究3-甲醛吡喃酮衍生物的可能作用机制，还进行了分子对接研究，结果显示，所研究的化合物很好地适应hTopo-IIα酶的ATP结合口袋，具有良好的对接分数，并与催化位点的关键残基形成非键相互作用。
• Mechanism of unusual formation of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides and their antimicrobial evaluation
  作者：Tilak Raj、Richa Kaur Bhatia、Rakesh Kumar Sharma、Vivek Gupta、Deepak Sharma、Mohan Paul Singh Ishar

  DOI：10.1016/j.ejmech.2009.03.030

  日期：2009.8

  6/6,7-Substituted 3-formylchromones (9a-e) react with 2 equivalents of 2-phenyl-4-dimethylamino-1-thia-3-azabuta-1,3-diene (10) or thiobenzamide (11) in refluxing toluene to furnish novel substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (12a-e). However, reactions of substituted 2-anilino-3-formylchromones (15a-d) with thiobenzamide (11, 2 equivalents) in refluxing xylene furnish 4-oxo-4H-chromene-3-carbothioic acid N-phenylamide (17a-d) in high yields. A mechanistic rationalization of the conversion of 2-anilino-3-formylchromones (15a-d) to N-phenylamides (17a-d), and 3-formylchromones (9a-e) to the corresponding thioaldehydes, is proffered. All the compounds (12a-e, 17a-d) display very high antifungal and antibacterial activities against a number of strains. Dithiazole 12d exhibits a very high antifungal activity (MIC 5 mu g/ml) against Geotrichum candidum, better than fluconazole (MIC 09 mu g/ml) and also possesses good antibacterial activity (MIC 52 mu g/ml) against Shigella flexneri. (C) 2009 Elsevier Masson SAS. All rights reserved.