N-(4-bromophenyl)-2-oxo-2H-chromene-3-carboxamide | 74555-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-bromophenyl)-2-oxo-2H-chromene-3-carboxamide
• 英文别名: N-(4-bromophenyl)-2-oxochromene-3-carboxamide
• CAS: 74555-99-0
• 化学式: C₁₆H₁₀BrNO₃
• mdl: MFCD00249912
• 分子量: 344.164
• InChiKey: MPFQLHJYNVDUEK-UHFFFAOYSA-N

物化性质

• 熔点：
  269-271 °C
• 沸点：
  574.1±50.0 °C(Predicted)
• 密度：
  1.639±0.06 g/cm3(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：
  2
• 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：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-bromophenyl)-2-oxo-2H-chromene-3-carboxamide 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 8.5h， 生成 N-(4-Bromo-phenyl)-2-[1-phenyl-meth-(E)-ylidene-hydrazinocarbonyl]-acetamide
  参考文献：
  名称：

  Islam, A. M.; Bedair, A. H.; Aly, F. M., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 3, p. 224 - 226

  摘要：

  DOI：
• 作为产物：
  描述：

  N-phenyl-2-oxochromene-3-carboxamide 在 溴 作用下， 以 氯仿 为溶剂， 生成 N-(4-bromophenyl)-2-oxo-2H-chromene-3-carboxamide
  参考文献：
  名称：

  Islam, A. M.; Bedair, A. H.; Aly, F. M., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 3, p. 224 - 226

  摘要：

  DOI：

文献信息

• Design, Synthesis and In Vitro Evaluation of 2-Oxo-N-substituted Phenyl- 2H-chromene-3-carboxamide Derivatives as HIV Integrase Strand Transfer Inhibitors
  作者：Pankaj Wadhwa、Priti Jain、Hemant R. Jadhav

  DOI：10.2174/1570180816666190617150803

  日期：2020.4.25

  been evaluated for HIV-1 integrase (IN) inhibition. Methods: The derivatives were synthesized via a two-step pathway commencing with 2- hydroxybenzaldehyde and diethyl malonate followed by hydrolysis of ester and coupling with various aromatic amines. The HIV-1 IN inhibitory potential of these compounds has been studied relative to dolutegravir, a known HIV-1 IN inhibitor using a standard available

  背景：已经评估了一系列18个2-氧-N-取代的苯基-2H-色烯-3-羧酰胺类似物对HIV-1整合酶（IN）的抑制作用。 方法：衍生物是通过两步途径从2-羟基苯甲醛和丙二酸二乙酯开始合成，然后将酯水解并与各种芳香胺偶联。已使用标准可用试剂盒相对于已知的HIV-1 IN抑制剂dolutegravir研究了这些化合物的HIV-1 IN抑制潜力。 结果：六个分子（化合物13h，13i，13l，13p至13r）显示出对HIV-1整合酶3'链转移的显着抑制作用，IC50值小于1.7μM。苯甲基-3-羧酰胺基序的存在对酶活性至关重要。此外，还进行了分子建模研究以证明IN抑制的合理性，并得出了体外-计算机相关性。 结论：然而，这些化合物在其细胞毒性浓度以下均未显示HIV-1和HIV-2抑制作用，表明这些化合物无法进一步用于抗HIV活性，因此需要进行结构修饰。
• Coumarins and adenosine receptors: New perceptions in structure-affinity relationships
  作者：André Fonseca、Maria João Matos、Santiago Vilar、Sonja Kachler、Karl-Norbert Klotz、Eugenio Uriarte、Fernanda Borges

  DOI：10.1111/cbdd.13075

  日期：2018.1

  Adenosine receptor (AR) subtypes are involved in several physiological and pharmacological processes. Ligands that are able to selectively modulate one receptor subtype can delay or slow down the progression of diverse diseases. In this context, our research group focused its investigation into the discovery and development of novel, potent and selective AR ligands based on coumarin scaffold. Therefore

  腺苷受体（AR）亚型涉及几种生理和药理过程。能够选择性调节一种受体亚型的配体可以延缓或减缓多种疾病的发展。在这种情况下，我们的研究小组将研究重点放在了基于香豆素骨架的新型，有效和选择性AR配体的发现和开发上。因此，一系列的3-phenylcarboxamidocoumarins合成以及它们在人AR亚型的亲和性是通过放射性配体结合测定法用于筛选阿1，A 2A和A 3个受体和对于A 2B由腺苷酸环化酶测定。发现化合物26最显着，其h A1 / ħ甲3和ħ甲2A / ħ甲3选择性的42，为A 3 AR（ķ我 = 2.4μ米）。受体驱动的分子建模研究为化合物26的结合/选择性数据以及随后的优化过程提供了有价值的信息。此外，化合物26根据与该概念有关的一般指导原则表现出药物样性质。
• Cyclopropanation of N-Substituted 2-Oxochromene- and 6-Bromo-2-oxochromene-3-carboxamides with Zinc Enolates Derived from 1-Aryl-2,2-dibromoalkanones
  作者：V. V. Shchepin、P. S. Silaichev、R. V. Shchepin、M. A. Ezhikova、M. I. Kodess

  DOI：10.1007/s11178-005-0199-6

  日期：2005.4

  Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-cyclohexyl-2-oxochromene-3-carboxamides to give N-cyclohexyl-1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides mainly as cis isomers with respect to the substituents in positions 1 and 1a. Reactions of the same zinc enolates with N-benzyl-2-oxochromene-3-carboxamide and N-benzyl-6-bromo-2-oxochromene-3-carboxamide lead to formation of 1-aryl-2-benzyl- and 1-aryl-2-benzyl-6-bromo-1-hydroxy-9c-alkyl-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones. The reaction of zinc enolates with N-aryl-2-oxochromene-3-carboxamides in a weakly polar solvent (diethyl ether or ethyl acetate) affords mixtures of cis-N-aryl-1-aroyl-1-alkyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides and their cyclic isomers, 9c-alkyl-1,2-diaryl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones, the latter prevailing. N-Substituted 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides in which the aroyl group on C1 and the carboxamide group on C1a are arranged trans are formed by reactions of zinc enolates with the corresponding 2-oxochromene-3-carboxamides in the presence of hexamethylphosphoric triamide.

  源自1-芳基-2,2-二溴代烷基酮的锌烯醇盐与N-环己基-2-氧代色烯-3-羧酰胺反应，主要生成顺式异构体，相对于位置1和1a的取代基，形式为N-环己基-1-烷基-1-芳酰基-2-氧代-1a,7b-二氢环丙[c]色烯-1a-羧酰胺。同样的锌烯醇盐与N-苄基-2-氧代色烯-3-羧酰胺和N-苄基-6-溴-2-氧代色烯-3-羧酰胺反应，生成1-芳基-2-苄基和1-芳基-2-苄基-6-溴-1-羟基-9c-烷基-1,2,9b,9c-四氢-5-氧-2-氮杂环戊[2,3]环丙[1,2-a]萘-3,4-二酮。锌烯醇盐与N-芳基-2-氧代色烯-3-羧酰胺在弱极性溶剂（乙醚或乙酸乙酯）中反应，得到顺式N-芳基-1-芳酰基-1-烷基-2-氧代-1a,7b-二氢环丙[c]色烯-1a-羧酰胺及其环状异构体，即9c-烷基-1,2-二芳基-1-羟基-1,2,9b,9c-四氢-5-氧-2-氮杂环戊[2,3]环丙[1,2-a]萘-3,4-二酮，后者占优势。在六甲基磷酸三胺存在下，锌烯醇盐与相应的2-氧代色烯-3-羧酰胺反应，生成N-取代的1-烷基-1-芳酰基-2-氧代-1a,7b-二氢环丙[c]色烯-1a-羧酰胺，其中C1上的芳酰基和C1a上的羧酰胺基团以反式排列。
• 1,1'-Carbonyldiimidazole (CDI) Mediated Facile Synthesis, Structural Characterization, Antimicrobial Activity, and in-silico Studies of Coumarin- 3-carboxamide Derivatives
  作者：Uzma Salar、Khalid M. Khan、Muhammad I. Fakhri、Shafqat Hussain、Saima Tauseef、Shagufta Ameer、Abdul Wadood、Huma Khan、Shahnaz Perveen

  DOI：10.2174/1573406413666170623083116

  日期：2018.1.11

  Background: Despite the availability of a variety of antibacterial agents, re-emergence of pathogenic bacteria is still a serious medical concern. So, identification of new, safer, and selective antibacterial agents is the key interest in the medicinal chemistry research. Method: To explore the antimicrobial activity of coumarin-3-carboxamides for a range of bacterial and fungal strains, twenty eight derivatives were synthesized by the reaction of coumarin-3-carboxylic acid with a variety of aniline derivatives in the presence of 1,1'-carbonyldiimidazole (CDI). All compounds were structurally characterized by different spectroscopic techniques EI-MS, HREI-MS, 1H-NMR, 13C-NMR, and evaluated for antimicrobial activities (antibacterial and antifungal). Results: A number of compounds showed good to weak antibacterial activity against various strains of Gram-positive and Gram-negative bacteria. Amongst them, compound 28 displayed noticeable inhibition against five strains of Gram-positive (Bacillus subtilis, Corynebacterium xerosis, Staphylococcus aureus, Streptococcus faecalis, and MRSA) and four strains of Gram-negative bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogene, and Shigella dysenteria). However, none of the compounds showed antifungal activity against tested fungi. MIC values were determined for most of the active compounds 2, 15, and 28 against particular bacterial cultures. In silico studies were performed on the most active compound 28 in order to specify and verify the target for antibacterial activity of synthetic coumarin-3-carboxamide derivatives. The cytotoxicity of these compounds on mammalian cells is unknown yet but we are planning to carry out research on the cytotoxic aspect of these compounds in future. Conclusion: The newly identified compounds may serve as lead molecules for the future research regarding the identification of new antibacterial agents.

  背景：尽管已有多种抗菌剂可用，但致病菌的重新出现仍然是一个严重的医学问题。因此，鉴定新型更安全和选择性的抗菌剂是药物化学研究的关键兴趣。 方法：为了探索香豆素-3-羧酰胺对多种细菌和真菌菌株的抗微生物活性，通过将香豆素-3-羧酸与多种苯胺衍生物在1,1'-羰基二咪唑（CDI）存在下反应合成了28种衍生物。所有化合物均采用不同的光谱技术（EI-MS、HREI-MS、1H-NMR、13C-NMR）进行结构表征，并评估其抗微生物活性（抗菌和抗真菌）。 结果：多种化合物对不同的革兰阳性和革兰阴性菌株显示良好到弱的抗菌活性。其中，化合物28对五种革兰阳性菌（枯草芽孢杆菌、干燥棒状杆菌、金黄色葡萄球菌、屎肠球菌和耐甲氧西林金黄色葡萄球菌）和四种革兰阴性细菌（肺炎克雷伯菌、铜绿假单胞菌、嗜麦芽窄食杆菌和志贺菌）表现出显著的抑制作用。然而，所有化合物在测试的真菌中均未显示抗真菌活性。对大多数活性化合物2、15和28在特定细菌培养物上的最低抑菌浓度（MIC）进行了测定。针对最活跃的化合物28进行了分子模拟研究，以明确和验证合成香豆素-3-羧酰胺衍生物的抗菌活性靶点。这些化合物对哺乳动物细胞的细胞毒性尚未确定，但我们计划在未来对这些化合物的细胞毒性方面进行研究。 结论：新鉴定的化合物可作为未来研究新抗菌剂的先导分子。
• Synthesis of 3-R1-1-R2-1-R3-4a,10b-dihydro-1H-chromeno[3,4-c]-pyridine-2,4,5-triones by the Reformatskii reaction
  作者：V. V. Shchepin、D. V. Fotin、M. I. Vakhrin、S. N. Shurov

  DOI：10.1007/s11176-005-0021-8

  日期：2004.9

  The Reformatskii reagents formed from alkyl esters of α-bromoacetic, α-bromopropanoic, and α-bromoisobutyric acids and zinc react with N -arylamides of 2-oxochromene-3-carboxylic acid, yielding 3-R1-1-R2-1-R3-4a,10b-dihydro-1 H -chromeno[3,4- c ]pyridine-2,4,5-triones.

  由α-溴乙酸，α-溴丙酸和α-溴异丁酸的烷基酯与锌形成的Reformatskii试剂与 2-氧代色烯-3-羧酸的 N- 芳酰胺反应生成3-R 1 -1-R 2 -1 -R 3 -4a，10b-二氢-1 H- 苯并[3,4- c ]吡啶-2,4,5-三酮。