2-amino-4-(2,4-dimethoxyphenyl)-4H-benzo[h]chromene-3-carbonitrile | 303139-15-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: 2-amino-4-(2,4-dimethoxyphenyl)-4H-benzo[h]chromene-3-carbonitrile
• CAS: 303139-15-3
• 化学式: C₂₂H₁₈N₂O₃
• 分子量: 358.397
• InChiKey: HDDYCMPDTFLIKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-4-(2,4-dimethoxyphenyl)-4H-benzo[h]chromene-3-carbonitrile 在 偶氮二甲酸二异丙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以84%的产率得到4-(2,4-Dimethoxyphenyl)-2-iminobenzo[h]chromene-3-carbonitrile
  参考文献：
  名称：

  偶氮二羧酸二异丙酯介导的2-氨基-3-氰基4 H-色烯的选择性脱氢

  摘要：

  据报道，在中性条件下，由偶氮二羧酸二异丙酯介导的2-氨基-3-氰基4 H-色酮选择性脱氢为相应的2-亚氨基色酮。脱氢反应与酚羟基相容并以高收率产生亚氨基色烯。该方法提供了香豆素和N-甲苯磺酰基2-氨基-3-氰基-4-芳基4 H-色烯的容易获得。

  DOI：

  10.1016/j.tetlet.2017.03.049
• 作为产物：
  描述：

  萘酚 、 2-(2,4-二甲氧基苄亚基)丙二腈 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以63%的产率得到2-amino-4-(2,4-dimethoxyphenyl)-4H-benzo[h]chromene-3-carbonitrile
  参考文献：
  名称：

  Synthesis, biological assessment, and molecular modeling of racemic 7-aryl-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-b]quinolin-8-amines as potential drugs for the treatment of Alzheimer's disease

  摘要：

  The synthesis, pharmacological analysis and molecular modeling of the readily available racemic tacrine analogs 21-30, bearing the 7-aryl-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-b[quinolin-8-amine heterocyclic ring system (II), prepared by Friedlander reaction of 2-amino-4-aryl-4H-benzo[h] chromene-3-carbonitriles (11-20) with cyclohexanone, are described in this paper. Molecules 21-30 are potent and selective inhibitors of hAChE, in the low micromolar range, one of the most potent inhibitors, 4-(8-amino-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-blquinolin-7-y1)-2-methoxyphenol (25), showing a IC50 (hAChE) = 0.33 +/- 0.04 mu M. Kinetic studies of compound 25 proved that this compound is a mixed type inhibitor for EeAChE (K-i=81 nM). Accordingly, molecular modeling of inhibitor 25 showed that both enantiomers have two major predicted binding modes at the active and at the peripheral anionic sites of AChE. Inhibitor 25 has an excellent antioxidant profile as determined in the ORAC experiment (1.47 +/- 0.10 Trolox equiv). Inhibitors 26-28 and 30 are permeable to BBB as determined in the PAMPA assay. Compared to tacrine, selected compounds 26-28 and 30 showed less hepatic toxicity in HepG2 cells. Moreover, cell viability-related studies in cortical neurons in primary cultures show that compounds 26-28 and 30 (0.1-50 mu M) have significant neuroprotective effects against mitochondrial chain blockers-induced cell death, and, unlike tacrine, are not neurotoxic at concentrations lower than 50 mu M. It is worth highlighting that compound 27 has the best neuroprotective properties out of all assayed compounds and shows no neurotoxicity. To sum up, these tacrine analogs can be considered as attractive multipotent therapeutic molecules on pharmacological receptors playing key roles in the progress of Alzheimer's disease. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.038

文献信息

• Fe₃O₄‐supported sulfonated graphene oxide as a green and magnetically separable nanocatalyst for synthesis of 2-amino-3-cyano-4<i>H-</i>chromene derivatives and their in-silico studies
  作者：Shaily Sharma、Mahesh Meena、Himanshu Sharma、Dinesh Kumar Yadav、Atul Tiwari、Ved Prakash Verma

  DOI：10.1080/00397911.2022.2120404

  日期：2022.10.18

  Highlights Room temperature and ultrasound assisted three-component synthesis Synthesis of biological important 4H-chromene derivatives in H2O: EtOH (1:1) solvent High yields of products (88–95%) within rapid reaction time (10–15 min). High atom economy 95%. Avoid of column chromatography In-silico studies Easy and fast work up Magnetically separable and reusable catalyst.

  摘要 在超声照射下，通过脂肪/芳香/杂环醛、丙二腈和α-萘酚/β-的一锅三组分多米诺 Knoevenagel-Michael 缩合反应制备了 17 个 2-Amino-3-cyano-4H-chromene 衍生物。萘酚/间苯二酚在 Fe 3 O 4负载的磺化氧化石墨烯存在下作为 H 2中的绿色磁性可分离纳米催化剂O: EtOH (1:1) 溶剂系统。FT-IR、TGA、SEM和XRD用于评估催化剂。目前的协议具有吸引力，因为原子经济性高（95%）、产率高（88-95%）、反应时间短、无废物条件、成本效益高、使用无毒溶剂、无需高温回流, 产品的非色谱纯化, 催化剂的可回收性等。对选定的蛋白质 DNA 旋转酶 (1KZN) 和 CYP51 (4WMZ) 进行了计算机研究, 以研究最高对接分数4h (-8.8 kcal/mol ) 的对接相互作用) 和4e (-10.1 kcal/mol)。还进行了对接化合物和参考药物的
• Diisopropyl azodicarboxylate mediated selective dehydrogenation of 2-amino-3-cyano 4 H -chromenes
  作者：Himanshu Sharma、Mohini Mourya、Debanjan Guin、Yogesh C. Joshi、Mahabeer P. Dobhal、Ashok K. Basak

  DOI：10.1016/j.tetlet.2017.03.049

  日期：2017.5

  Selective dehydrogenation of 2-amino-3-cyano 4H-chromenes to the corresponding 2-iminochromenes mediated by diisopropyl azodicarboxylate under neutral conditions is reported. The dehydrogenation reaction is compatible with phenolic hydroxyl group and generates iminochromene in high yields. The methodology provides an easy access to coumarin and N-tosyl 2-amino-3-cyano-4-aryl 4H-chromenes.

  据报道，在中性条件下，由偶氮二羧酸二异丙酯介导的2-氨基-3-氰基4 H-色酮选择性脱氢为相应的2-亚氨基色酮。脱氢反应与酚羟基相容并以高收率产生亚氨基色烯。该方法提供了香豆素和N-甲苯磺酰基2-氨基-3-氰基-4-芳基4 H-色烯的容易获得。
• Synthesis, biological assessment, and molecular modeling of racemic 7-aryl-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-b]quinolin-8-amines as potential drugs for the treatment of Alzheimer's disease
  作者：Emna Maalej、Fakher Chabchoub、María Jesús Oset-Gasque、Mario Esquivias-Pérez、María P. González、Leticia Monjas、Concepción Pérez、Cristóbal de los Ríos、María Isabel Rodríguez-Franco、Isabel Iriepa、Ignacio Moraleda、Mourad Chioua、Alejandro Romero、José Marco-Contelles、Abdelouahid Samadi

  DOI：10.1016/j.ejmech.2012.06.038

  日期：2012.8

  The synthesis, pharmacological analysis and molecular modeling of the readily available racemic tacrine analogs 21-30, bearing the 7-aryl-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-b[quinolin-8-amine heterocyclic ring system (II), prepared by Friedlander reaction of 2-amino-4-aryl-4H-benzo[h] chromene-3-carbonitriles (11-20) with cyclohexanone, are described in this paper. Molecules 21-30 are potent and selective inhibitors of hAChE, in the low micromolar range, one of the most potent inhibitors, 4-(8-amino-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-blquinolin-7-y1)-2-methoxyphenol (25), showing a IC50 (hAChE) = 0.33 +/- 0.04 mu M. Kinetic studies of compound 25 proved that this compound is a mixed type inhibitor for EeAChE (K-i=81 nM). Accordingly, molecular modeling of inhibitor 25 showed that both enantiomers have two major predicted binding modes at the active and at the peripheral anionic sites of AChE. Inhibitor 25 has an excellent antioxidant profile as determined in the ORAC experiment (1.47 +/- 0.10 Trolox equiv). Inhibitors 26-28 and 30 are permeable to BBB as determined in the PAMPA assay. Compared to tacrine, selected compounds 26-28 and 30 showed less hepatic toxicity in HepG2 cells. Moreover, cell viability-related studies in cortical neurons in primary cultures show that compounds 26-28 and 30 (0.1-50 mu M) have significant neuroprotective effects against mitochondrial chain blockers-induced cell death, and, unlike tacrine, are not neurotoxic at concentrations lower than 50 mu M. It is worth highlighting that compound 27 has the best neuroprotective properties out of all assayed compounds and shows no neurotoxicity. To sum up, these tacrine analogs can be considered as attractive multipotent therapeutic molecules on pharmacological receptors playing key roles in the progress of Alzheimer's disease. (C) 2012 Elsevier Masson SAS. All rights reserved.