3-amino-1-(3,4,5-trimethoxyphenyl)-1H-benzo[f]chromene-2-carbonitrile | 299198-80-4

• 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: 3-amino-1-(3,4,5-trimethoxyphenyl)-1H-benzo[f]chromene-2-carbonitrile
• 英文别名: 2-amino-4-(3,4,5-trimethoxyphenyl)naphtho[2,1-b]-4H-pyran-3-carboxaldehyde
• CAS: 299198-80-4
• 化学式: C₂₃H₂₀N₂O₄
• 分子量: 388.423
• InChiKey: PDKVWSUNRQULDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-amino-1-(3,4,5-trimethoxyphenyl)-1H-benzo[f]chromene-2-carbonitrile 在 溶剂黄146 作用下， 生成 N-(1-benzylpiperidin-4-yl)-12-(3,4,5-trimethoxyphenyl)-12H-benzo[5,6]chromeno[2,3-d]pyrimidin-11-amine
  参考文献：
  名称：

  新型氨基嘧啶衍生物的细胞毒活性和DNA结合特性

  摘要：

  背景：Chromene和苯胺嘧啶杂环化合物是有吸引力的抗癌化合物，它激发了许多研究人员设计具有改善抗癌活性的新型衍生物。 方法：合成了一系列嘧啶稠合的苯并[f]苯甲基衍生物6a-x，作为1H-苯并[f]苯甲基和苯胺嘧啶的抗癌混合物。使用MTT分析评估了合成的化合物6a-x对人慢性骨髓性白血病（K562），人急性淋巴细胞性白血病（MOLT-4）和人乳腺腺癌（MCF-7）细胞系的抑制活性。还使用光谱滴定和圆二色谱（CD）光谱研究了最有希望的化合物与小牛胸腺DNA的相互作用。 结果：大多数化合物对测试的细胞系显示出有希望的活性。其中，2,4-二甲氧基苯胺基衍生物6g表现出对受试细胞系（IC50s = 1.6-6.1μM）的最佳活性，对NIH3T3正常细胞无毒性（IC50> 200μM）。光谱研究表明，化合物6g牢固地与DNA结合，并可能显着改变DNA构象，大概是通过凹槽结合机制。 结论：本研究结

  DOI：

  10.2174/1570180816666190712102119
• 作为产物：
  描述：

  [(3,4,5-三甲氧基苯基)亚甲基]丙二腈 、 2-萘酚 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 3-amino-1-(3,4,5-trimethoxyphenyl)-1H-benzo[f]chromene-2-carbonitrile
  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

• Synthesis, screening and docking of fused pyrano[3,2- d ]pyrimidine derivatives as xanthine oxidase inhibitor
  作者：Manroopraj Kaur、Amandeep Kaur、Suhani Mankotia、Harbinder Singh、Arshdeep Singh、Jatinder Vir Singh、Manish Kumar Gupta、Sahil Sharma、Kunal Nepali、Preet Mohinder Singh Bedi

  DOI：10.1016/j.ejmech.2017.03.002

  日期：2017.5

  In view of developing effective xanthine oxidase (XO) enzyme inhibitors, a series of 100 pyrano[3,2-d]pyrimidine derivatives was synthesized and evaluated for its in vitro XO enzyme inhibition. Structure activity relationship has also been established. Among all the synthesized compounds, 4d, 8d and 9d were found to be the most potent enzyme inhibitors with IC50 values of 8μM, 8.5μM and 7μM, respectively

  鉴于开发有效的黄嘌呤氧化酶（XO）酶抑制剂，合成了一系列100种吡喃并[3,2-d]嘧啶衍生物，并对其体外XO酶抑制进行了评估。结构活动关系也已建立。在所有合成的化合物中，发现4d，8d和9d是最有效的酶抑制剂，IC50值分别为8μM，8.5μM和7μM。在酶动力学研究中进一步研究了化合物9d，Lineweaver-Burk图显示化合物9d是混合型抑制剂。还已经计算出最有效的化合物4d，8d和9d的分子性质。进行了对接研究以研究黄嘌呤氧化酶与最有效的XO抑制剂9d之间的识别模式。
• Basic Magnetic Nanoparticles as Efficient Catalysts for the Preparation of Naphthopyrane Derivatives
  作者：Hossein Yarahmadi、Hamid Reza Shaterian

  DOI：10.3184/174751912x13264750348839

  日期：2012.1

  Aminosilane-functionalised spinel ferrite oxide (Fe2O3) magnetic nanoparticles have been synthesised and used as efficient heterogeneous base catalysts for the condensation of aromatic aldehydes with malonitrile and α (or β) naphthole via a three-component reaction under solvent-free conditions at 80°C. Quantitative conversion of the reactants is achieved under mild conditions. Recovery of the catalyst is easily achieved

  氨基硅烷官能化的尖晶石氧化铁氧体 (Fe2O3) 磁性纳米粒子已被合成并用作有效的多相碱催化剂，用于在 80°无溶剂条件下通过三组分反应使芳香醛与丙二腈和α（或β）萘酚缩合C。在温和条件下实现反应物的定量转化。通过磁倾析很容易实现催化剂的回收。负载型催化剂可重复使用四次，催化活性没有显着降低。萘并吡喃是具有许多生物学和药理学特性的多功能化苯并吡喃衍生物。
• 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.
• Mahmoud; Shalaby; Gad, Egyptian Journal of Chemistry, 2008, vol. 51, # 6, p. 879 - 888
  作者：Mahmoud、Shalaby、Gad、El-Khamry

  DOI：——

  日期：——
• Cytotoxic Activity and DNA Binding Property of New Aminopyrimidine Derivatives
  作者：Hamidreza Akrami、Bibi Fatemeh Mirjalili、Omidreza Firuzi、Azadeh Hekmat、Ali Akbar Saboury、Ramin Miri、Omid Sabzevari、Morteza Pirali-Hamedani、Fereshteh Jeivad、Setareh Moghimi、Saeed Emami、Alireza Foroumadi、Mehdi Khoobi

  DOI：10.2174/1570180816666190712102119

  日期：2020.5.18

  attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved anticancer activity. Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the synthesized compounds 6a-x against cell viability of human chronic myelogenous leukemia

  背景：Chromene和苯胺嘧啶杂环化合物是有吸引力的抗癌化合物，它激发了许多研究人员设计具有改善抗癌活性的新型衍生物。 方法：合成了一系列嘧啶稠合的苯并[f]苯甲基衍生物6a-x，作为1H-苯并[f]苯甲基和苯胺嘧啶的抗癌混合物。使用MTT分析评估了合成的化合物6a-x对人慢性骨髓性白血病（K562），人急性淋巴细胞性白血病（MOLT-4）和人乳腺腺癌（MCF-7）细胞系的抑制活性。还使用光谱滴定和圆二色谱（CD）光谱研究了最有希望的化合物与小牛胸腺DNA的相互作用。 结果：大多数化合物对测试的细胞系显示出有希望的活性。其中，2,4-二甲氧基苯胺基衍生物6g表现出对受试细胞系（IC50s = 1.6-6.1μM）的最佳活性，对NIH3T3正常细胞无毒性（IC50> 200μM）。光谱研究表明，化合物6g牢固地与DNA结合，并可能显着改变DNA构象，大概是通过凹槽结合机制。 结论：本研究结