2-amino-4-(2,6-dichlorophenyl)-4H-benzo[h]chromene-3-carbonitrile | 346436-66-6

• 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-(2,6-dichlorophenyl)-4H-benzo[h]chromene-3-carbonitrile
• CAS: 346436-66-6
• 化学式: C₂₀H₁₂Cl₂N₂O
• 分子量: 367.234
• InChiKey: DQTAILKGJGQHKJ-UHFFFAOYSA-N

物化性质

• 沸点：
  547.8±50.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-4-(2,6-dichlorophenyl)-4H-benzo[h]chromene-3-carbonitrile 、 乙酸酐 在 硫酸 、 水 作用下， 反应 0.22h， 以70%的产率得到7-(2,6-dichlorophenyl)-10-methyl-7H-benzo[7,8]chromeno[2,3-d]pyrimidin-8(9H)-one
  参考文献：
  名称：

  四环吡喃并[2,3-d]嘧啶的高效合成

  摘要：

  通过2-氨基-3-氰基-4- H-吡喃与乙酸酐与酸催化剂的反应合成了一系列吡喃并[2,3- d ]嘧啶衍生物。该方法由于反应时间短且易于后处理而非常有效，并且为构建四环吡喃并[2,3- d ]嘧啶骨架提供了有效而有前途的合成策略。确认了产品的X射线晶体结构，并提供了可能的机理。

  DOI：

  10.1002/jhet.2630
• 作为产物：
  描述：

  萘酚 、 2,6-二氯苯亚甲基丙二腈 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以81%的产率得到2-amino-4-(2,6-dichlorophenyl)-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

• An Efficient Synthesis of Tetracyclic Pyrano[2,3-<i>d</i>]pyrimidines
  作者：Zhi-Lan Lin、Jun-Min Zhang、Yuan Gao

  DOI：10.1002/jhet.2630

  日期：2017.1

  A series of pyrano[2,3‐d]pyrimidine derivatives have been synthesized by the reaction of 2‐amino‐3‐cyano‐4H‐pyrans and acetic anhydride with acid catalyst . This method is very efficient because of short reaction times and easy work‐up, and it provides an efficient and promising synthetic strategy for the construction of the tetracyclic pyrano[2,3‐d]pyrimidine skeleton. The X‐ray crystal structures

  通过2-氨基-3-氰基-4- H-吡喃与乙酸酐与酸催化剂的反应合成了一系列吡喃并[2,3- d ]嘧啶衍生物。该方法由于反应时间短且易于后处理而非常有效，并且为构建四环吡喃并[2,3- d ]嘧啶骨架提供了有效而有前途的合成策略。确认了产品的X射线晶体结构，并提供了可能的机理。
• 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.