2-amino-4-(4-chlorophenyl)-7-dimethylamino-4H-chromene-3-carbonitrile | 797028-49-0

• 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-(4-chlorophenyl)-7-dimethylamino-4H-chromene-3-carbonitrile
• 英文别名: 2-amino-4-(4-chlorophenyl)-7-(dimethylamino)-4H-chromene-3-carbonitrile
• CAS: 797028-49-0
• 化学式: C₁₈H₁₆ClN₃O
• 分子量: 325.798
• InChiKey: LRLGWJMPJIVGBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯苄亚基丙二腈 、 3-羟基-N,N-二甲基苯胺 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 2-amino-4-(4-chlorophenyl)-7-dimethylamino-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationship (SAR) Studies on some 4-Aryl-4Hchromenes and Relationship between Lipophilicity and Antitumor Activity

  摘要：

  通过3-取代酚1、4、6和8与α-氰基肉桂腈衍生物2的反应，获得了一些4-芳基-4H-色烯3a-h、5a-g、7a-g和9a-g。我们探讨了在4-和7-位进行修饰的4-芳基-4H-色烯的结构-活性关系（SAR）。使用微培养四唑盐（MTT）比色法，与标准药物长春碱和多柔比星相比，研究了合成的化合物的抗肿瘤活性。一些化合物显示出良好的体外抗肿瘤活性。结构-活性关系（SAR）研究发现，4-芳基-4H-色烯的抗肿瘤活性显著受到亲脂性、计算得到的Log P值以及7-亲水或疏水取代基与4-位苯环上的疏水取代基之间的平衡的影响。新制备的化合物的结构通过元素分析和光谱数据得到了确认。

  DOI：

  10.2174/1570180811666140623204655

文献信息

• Tris-hydroxymethylaminomethane (THAM): a novel organocatalyst for a environmentally benign synthesis of medicinally important tetrahydrobenzo[b]pyrans and pyran-annulated heterocycles
  作者：Kapil S. Pandit、Pramod V. Chavan、Uday V. Desai、Makarand A. Kulkarni、Prakash P. Wadgaonkar

  DOI：10.1039/c4nj02346c

  日期：——

  A simple, efficient and environmentally benign protocol has been developed for the one-pot, multicomponent synthesis of medicinally important tetrahydrobenzo[b]pyrans and pyran-annulated heterocycles using a commercially available, inexpensive, non-toxic, and biodegradable tris-hydroxymethylaminomethane (THAM) as a novel organocatalyst. Ambient reaction conditions, wide scope, avoidance of conventional

  已经开发了一种简单，有效且对环境无害的方案，用于使用市售，廉价，无毒且可生物降解的三羟甲基甲基甲烷（THAM）一锅，多组分合成重要的药用四氢苯并[ b ]吡喃和吡喃环杂环）作为新型有机催化剂。环境反应条件，宽范围，避免常规分离以及纯化技术以及催化剂连续五次运行的可重复使用性提高了该多组分反应规程歧管的实用性。
• Organocatalytic Cascade Knoevenagel–Michael Addition Reactions: Direct Synthesis of Polysubstituted 2-Amino-4H-Chromene Derivatives
  作者：Sanjay N. Jadhav、Seema P. Patil、Dipti Prava Sahoo、Dharitri Rath、Kulamani Parida、Chandrashekhar V. Rode

  DOI：10.1007/s10562-019-03089-8

  日期：2020.8

  isotherms measurements, and they were successfully examined for the cascade type Knoevenagel–Michael addition reactions. The product yields associated with these substrates were optimized, and key reaction parameters affecting the yields were identified. The present catalytic method is simple and robust for diversity oriented synthesis which proceeds good to excellent yields without generating any hazards

  在本报告中，我们记录了在异质 Al-MCM-41-LDH@APTES (ALAM) 催化下合成生物活性多取代 2-氨基-4H-色胺衍生物的新策略。开发了一种合成程序来制备 Al-MCM-41-LDH@APTES (ALAM) 多相碱性催化剂。介孔 Al-MCM-41 通过已知的接枝化学通过层状双氢氧化物 (LDH) 纳米片和 (3-氨基丙基) 三乙氧基硅烷 (APTES) 部分作为碱性有机催化剂进行功能化。所得催化剂的外表面和层内都含有氨基官能团，并且可以通过加载 APTES 来调节碱度。通过 29Si 和 13C CP/MAS NMR、红外吸收光谱、TEM、XPS、EDX、TGA、XRD、CO2-TPD、N2 吸附等温线测量对样品进行了全面表征，并且他们成功地检测了级联型 Knoevenagel-Michael 加成反应。优化了与这些底物相关的产物产量，并确定了影响产量的关键反应参数。本
• Synthesis and characterization of a novel Fe₃O₄@SiO₂–BenzIm-Fc[Cl]/BiOCl nano-composite and its efficient catalytic activity in the ultrasound-assisted synthesis of diverse chromene analogs
  作者：Reza Mohammadi、Somayeh Esmati、Mahdi Gholamhosseini-Nazari、Reza Teimuri-Mofrad

  DOI：10.1039/c8nj04938f

  日期：——

  ultrasound-assisted synthesis protocol that was studied in this article exhibits some notable advantages such as short reaction times, operational simplicity, green reaction conditions, high yields and easy work-up and purification steps. In addition, the novel magnetic nano-composite could be easily recovered by an external magnetic field and reused for six-reaction cycles without significant loss of its catalytic

  在这项研究中，使用一种简单的化学共沉淀法合成了一种新型的可磁恢复的Fe 3 O 4 @SiO 2 -BenzIm-Fc [Cl] / BiOCl纳米复合材料。这是首次合成具有磁性纳米催化剂的离子液体，二茂铁和BiOCl。Fe 3 O 4 @SiO 2 -BenzIm-Fc [Cl] / BiOCl纳米复合材料的特点是通过傅里叶变换红外光谱（FT-IR），X射线衍射（XRD），能量色散X射线光谱（ EDX）和场发射扫描电子显微镜（FE-SEM）技术。在多种2-氨基-3-氰基-4的一锅三组分合成法中评估了新型磁性纳米复合材料的催化活性。超声辐照下的H-色烯衍生物。开发了一种简单，高效，高效的超声辅助方法，可通过以下方法合成4 H-色烯衍生物室温下，醛，丙二腈和活性酚类化合物（2-萘酚，1-萘酚，3-（二甲氨基）苯酚，间苯二酚和邻苯二酚）的一锅三组分反应。本文主要介绍了醛，丙二腈和草甘醇的反应。
• 4-Aryl-4H-Chromene-3-Carbonitrile Derivatives: Evaluation of Src Kinase Inhibitory and Anticancer Activities
  作者：Asal Fallah-Tafti、Rakesh Tiwari、Amir Nasrolahi Shirazi、Tahmineh Akbarzadeh、Deendayal Mandal、Abbas Shafiee、Keykavous Parang、Alireza Foroumadi

  DOI：10.2174/157340611796799258

  日期：2011.9.1

  Src kinase mutations and/or overexpression have been implicated in the development of a number of human cancers including colon, breast, and lung cancers. Thus, designing potent and selective Src kinase inhibitors as anticancer agents is a subject of major interest. A series of 4-aryl substituted derivatives of 2-amino-7-dimethylamino-4H-chromene- 3-carbonitrile were synthesized using one-pot reaction of appropriate substituted aromatic aldehydes, malononitrile, and 3-(dimethylamino)phenol in the presence of piperidine. All 23 compounds were evaluated for inhibition of Src kinase and cell proliferation in human colon adenocarcinoma (HT-29) and leukemia (CCRF-CEM) cell lines. Among the tested compounds, 2-chlorophenyl- (4c), 3-nitrophenyl- (4h), 4-trifluoromethyphenyl- (4i), and 2,3-dichlorophenyl- (4k) substituted chromenes showed Src kinase inhibitory effect with IC50 values of 11.1-18.3 μM. Compound 4c was relatively selective against Src (IC50 = 11.1 μM), when compared with selected kinases, epidermal growth factor receptor (EGFR, IC50 300 μM), C-terminal Src kinase (Csk, IC50 = 101.7 μM), and lymphocyte-specific protein tyrosine kinase (Lck, IC50 = 46.8 μM). 3-Chlorophenyl substituted thiazole (4v) and 2-chlorophenylsubstituted thiazole (4u) chromene derivatives inhibited the cell proliferation of HT-29 and CCRF-CEM by 80% and 50%, respectively, at a concentration of 50 μM. The data indicate that 4H-chromene-3-carbonitrile scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.

  Src 激酶突变和/或过度表达与结肠癌、乳腺癌和肺癌等多种人类癌症的发病有关。因此，设计强效且具有选择性的 Src 激酶抑制剂作为抗癌药物是一个备受关注的课题。在哌啶的存在下，利用适当取代的芳香醛、丙二腈和 3-（二甲基氨基）苯酚的一锅反应，合成了一系列 2-amino-7-dimethylamino-4H-chromene- 3-carbonitrile 的 4-芳基取代衍生物。对所有 23 种化合物在人结肠腺癌（HT-29）和白血病（CCRF-CEM）细胞系中对 Src 激酶和细胞增殖的抑制作用进行了评估。在测试的化合物中，2-氯苯基（4c）、3-硝基苯基（4h）、4-三氟甲基苯基（4i）和 2,3-二氯苯基（4k）取代的色烯类化合物具有抑制 Src 激酶的作用，IC50 值为 11.1-18.3 μM。与选定的激酶、表皮生长因子受体（EGFR，IC50 300 μM）、C-末端 Src 激酶（Csk，IC50 = 101.7 μM）和淋巴细胞特异性蛋白酪氨酸激酶（Lck，IC50 = 46.8 μM）相比，化合物 4c 对 Src 具有相对的选择性（IC50 = 11.1 μM）。3-氯苯基取代的噻唑（4v）和 2-氯苯基取代的噻唑（4u）色烯衍生物在 50 μM 浓度下分别抑制 HT-29 和 CCRF-CEM 细胞增殖 80% 和 50%。这些数据表明，4H-色烯-3-甲腈支架具有进一步优化的潜力，可用于设计更有效的 Src 激酶抑制剂和/或抗癌先导化合物。
• Synthesis, Structure-Activity Relationship (SAR) Studies on some 4-Aryl-4Hchromenes and Relationship between Lipophilicity and Antitumor Activity
  作者：Ahmed El-Agrody、Essam A. E. H. Khattab、Ahmed Fouda

  DOI：10.2174/1570180811666140623204655

  日期：2014.10.1

  Some 4-aryl-4H-chromenes 3a-h, 5a-g, 7a-g and 9a-g were obtained by reaction of 3-substituted phenol 1, 4, 6 and 8 with α-cyanocinnamonitrile derivatives 2. We explored the structure activity relationship (SAR) of 4-aryl-4Hchromenes with modification at the 4- and 7-positions. The antitumor activity of the synthesized compounds was investigated in comparison with the standard drugs Vinblastine and Doxorubicin using microculture tetrazolium (MTT) colorimetric assay. Some compounds were found to have good in vitro antitumor activity. The structure-activity relationship (SAR) study revealed that the antitumor activity of 4-aryl-4H-chromenes was significantly affected by the lipophilicity, the calculated Log P value and the balance between 7-hydrophilic or hydrophobic substituent and hydrophobic substituent on the benzene ring at 4-position. The structures of the newly prepared compounds were confirmed by elemental analysis and spectral data.

  通过3-取代酚1、4、6和8与α-氰基肉桂腈衍生物2的反应，获得了一些4-芳基-4H-色烯3a-h、5a-g、7a-g和9a-g。我们探讨了在4-和7-位进行修饰的4-芳基-4H-色烯的结构-活性关系（SAR）。使用微培养四唑盐（MTT）比色法，与标准药物长春碱和多柔比星相比，研究了合成的化合物的抗肿瘤活性。一些化合物显示出良好的体外抗肿瘤活性。结构-活性关系（SAR）研究发现，4-芳基-4H-色烯的抗肿瘤活性显著受到亲脂性、计算得到的Log P值以及7-亲水或疏水取代基与4-位苯环上的疏水取代基之间的平衡的影响。新制备的化合物的结构通过元素分析和光谱数据得到了确认。