4-[12-amino-9,10,11,13-tetrahydrobenzo[5,6]chromeno[2,3-b]cyclopenta[e]pyridin-13-yl]-2-methoxyphenol | 1300713-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 4-[12-amino-9,10,11,13-tetrahydrobenzo[5,6]chromeno[2,3-b]cyclopenta[e]pyridin-13-yl]-2-methoxyphenol
• 英文别名: 4-(10-Amino-2-oxa-4-azapentacyclo[11.8.0.03,11.05,9.014,19]henicosa-1(13),3,5(9),10,14,16,18,20-octaen-12-yl)-2-methoxyphenol
• CAS: 1300713-44-3
• 化学式: C₂₆H₂₂N₂O₃
• 分子量: 410.472
• InChiKey: JPZOSHNEWNUMJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-amino-1-(4-hydroxy-3-methoxyphenyl)-1H-benzo[f]chromene-2-carbonitrile 、 环戊酮 在 aluminum (III) chloride 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以25%的产率得到4-[12-amino-9,10,11,13-tetrahydrobenzo[5,6]chromeno[2,3-b]cyclopenta[e]pyridin-13-yl]-2-methoxyphenol
  参考文献：
  名称：

  Synthesis, biological assessment and molecular modeling of 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-13-amines

  摘要：

  The synthesis and pharmacological evaluation of racemic 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-13-amines (19-28), prepared by Friedlander reaction of 3-amino-1-aryl-1H-benzo[f]chromene-2-carbonitriles (10-18) with suitable cycloalkanones is described. These molecules are potent, in the nanomolar range [IC50 (EeAChE) = 7-101 nM], and selective inhibitors of acetylcholinesterase (AChE). The most potent inhibitor, 4-(13-amino-10,11,12,14-tetrahydro-9H-benzo[5,6] chromeno[2,3-b] quinolin-14-yl) phenol (20) [IC50 (EeAChE) = 7 +/- 2 nM] is four-fold more active than tacrine. Kinetic studies on compound 20 showed that this is a mixed-type inhibitor of EeAChE with a K-i of 5.00 nM. However, racemic 20 was unable to displace propidium iodide, suggesting that the inhibitor does not strongly bind to the peripheral anionic site (PAS) of AChE. Docking, molecular dynamics stimulations, and MM-GBSA calculations agree well with this behavior. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.094

文献信息

• Nontoxic and Neuroprotective β-Naphthotacrines for Alzheimer’s Disease
  作者：Mario Esquivias-Pérez、Emna Maalej、Alejandro Romero、Fakher Chabchoub、Abdelouahid Samadi、José Marco-Contelles、María Jesús Oset-Gasque

  DOI：10.1021/tx400138s

  日期：2013.6.17

  The synthesis, toxicity, neuroprotection, and human acetylcholinesterase (hAChE) / human butyrylcholinesterase (hBuChE) inhibition properties of beta-naphthotacrines 1-14 as new drugs for Alzheimer's disease (AD) potential treatment, are reported. beta-Naphthotacrines 1-14 showed lower toxicity than tacrine; moreover, at the highest concentration assayed (300 mu M) compounds 7, 10 and 11 displayed 2.25-2.01-fold higher cell viability than tacrine in HepG2 cells. A neuroprotective effect was observed for compounds 10 and 11 in a neuronal cortical culture exposed to a combination of oligomycin A/rotenone. An efficient and selective inhibition of hAChE, was only observed for the beta-naphthotacrines bearing electron-donating substituents at the aromatic ring, beta-naphthotacrine 10 being the most potent (hAChE: IC50 = 0.083 +/- 0.024 mu M). Kinetic inhibition analysis clearly demonstrated that beta-naphthotacrine 10 behaves as a mixed-type inhibitor (K-i2 = 0.72 +/- 0.06 mu M) at high substrate concentrations (0.5-10 mu M), while at low concentrations (0.01-0.1 mu M) it behaves as a hAChE competitive inhibitor (K-i1 = 0.007 +/- 0.001 mu M). These findings identified beta-naphthotacrine 10 as a potent and selective hAChE inhibitor in a nanomolar range, with toxicity lower than that of tacrine both in human hepatocytes and rat cortical neurons, with a potent neuroprotective activity and, consequently, an attractive multipotent active molecule of potential application in AD treatment.
• Synthesis, biological assessment and molecular modeling of 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-13-amines
  作者：Emna Maalej、Fakher Chabchoub、Abdelouahid Samadi、Cristóbal de los Ríos、Almudena Perona、Antonio Morreale、José Marco-Contelles

  DOI：10.1016/j.bmcl.2011.02.094

  日期：2011.4

  The synthesis and pharmacological evaluation of racemic 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-13-amines (19-28), prepared by Friedlander reaction of 3-amino-1-aryl-1H-benzo[f]chromene-2-carbonitriles (10-18) with suitable cycloalkanones is described. These molecules are potent, in the nanomolar range [IC50 (EeAChE) = 7-101 nM], and selective inhibitors of acetylcholinesterase (AChE). The most potent inhibitor, 4-(13-amino-10,11,12,14-tetrahydro-9H-benzo[5,6] chromeno[2,3-b] quinolin-14-yl) phenol (20) [IC50 (EeAChE) = 7 +/- 2 nM] is four-fold more active than tacrine. Kinetic studies on compound 20 showed that this is a mixed-type inhibitor of EeAChE with a K-i of 5.00 nM. However, racemic 20 was unable to displace propidium iodide, suggesting that the inhibitor does not strongly bind to the peripheral anionic site (PAS) of AChE. Docking, molecular dynamics stimulations, and MM-GBSA calculations agree well with this behavior. (C) 2011 Elsevier Ltd. All rights reserved.