benzyl 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate | 433967-29-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
• 英文别名: benzyl 6-methyl-2-oxo-4-(2-hydroxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate；6-methyl-4-(2-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid benzyl ester；benzyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 433967-29-4
• 化学式: C₁₉H₁₈N₂O₄
• 分子量: 338.363
• InChiKey: WBMFGBGMUKHVTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate 在 10% palladium on activated carbon 、 甲酸铵 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 4.5h， 以71%的产率得到9-methyl-8-oxa-10,12-diazatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene-11-one
  参考文献：
  名称：

  Synthesis of fused dihydro-pyrimido[4,3-d]coumarins using Biginelli multicomponent reaction as key step

  摘要：

  A new efficient approach for the synthesis of functionalized dihydro-pyrimido[4,3-d]coumarins is described. Use of benzyl- or tert-butyl acetoacetate and various salicyl aldehydes in typical Biginelli multicomponent reactions provides esters that can be easily deprotected to yield the corresponding hydroxy acids. Annelation of the latter leads to the target dihydro-pyrimido[4,3-d]coumarins. Formation of some unexpected oxo-bridged tetrahydro-pyrimidines is also described. Spectral properties of the synthesized dihydro-pyrimido[4,3-d]coumarins indicate the necessity to revisit some compounds previously reported as products of direct one-pot Biginelli condensation involving 4-hydroxycoumarin as dicarbonyl component. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.05.088
• 作为产物：
  描述：

  苯甲醇 在 cobalt hydrogen sulfate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 为溶剂， 生成 benzyl 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
  参考文献：
  名称：

  新型1,2,3,4-四氢嘧啶-5-羧酸衍生物的设计，合成和抗HIV-1评估。

  摘要：

  根据HIV-1 gp41结合位点抑制剂NB-2和NB-64的结构，设计，合成了一系列四氢嘧啶衍生物（2a-2l），并筛选了抗HIV-1特性。进行了一项计算研究，以预测所研究分子的药效动力学，药代动力学和类药物特征。对接研究表明，分子中的羧酸基与Lys574或Arg579形成盐桥。所合成化合物的理化性质（例如分子量，氢键供体的数目，氢键受体的数目和可旋转键的数目）证实并显示出这些化合物在李宾斯基五定律设定的范围内。在四氢嘧啶环的C（4）位置具有4-氯苯基取代基和4-甲基苯基的化合物2e和2k是最有效的化合物之一。这表明这些化合物可作为开发新型小分子HIV-1抑制剂的先导。

  DOI：

  10.1002/cbdv.201700502

文献信息

• Synthesis, biological evaluation and molecular docking study of dihydropyrimidine derivatives as potential anticancer agents
  作者：Sahand Safari、Reza Ghavimi、Nima Razzaghi‐Asl、Saghi Sepehri

  DOI：10.1002/jhet.3822

  日期：2020.3

  Subsequently, they were screened for in vitro anticancer effect. These analogues revealed good cytotoxic activity against three human cancer cell lines including MCF‐7, HepG‐2, and A549. Among these analogues, compounds 4d and 4h were the most potent against three cell lines. Cell viability assays indicated 4a and 4c had lower cytotoxicity. In vitro cytotoxicity study on all synthesized compounds demonstrated

  通过一锅Biginelli三组分缩合反应制备了一系列二氢嘧啶类似物，并通过NMR，FT-IR，MS光谱和元素分析进行​​了表征。随后，筛选它们的体外抗癌作用。这些类似物显示出对三种人类癌细胞系（包括MCF-7，HepG-2和A549）具有良好的细胞毒活性。在这些类似物中，化合物4d和4h对三种细胞系最有效。细胞活力测定表明4a和4c具有较低的细胞毒性。对所有合成化合物的体外细胞毒性研究表明，在二氢嘧啶苯环的C4位引入吸电子取代基有助于抑制增殖。此外，计算机分子对接的结果表明实验活性与计算的结合亲和力之间具有良好的相关性。事实证明4d和4h是最强的化合物。类似物的结合模式提出了疏水相互作用和具有Eg5活性位点的氢键的参与。结构活性关系研究表明，在二氢嘧啶苯环的C4位上引入吸电子取代基对于该生物活性很重要。
• Design, Synthesis, and Anti-HIV-1 Evaluation of a Novel Series of 1,2,3,4-Tetrahydropyrimidine-5-Carboxylic Acid Derivatives
  作者：Saghi Sepehri、Sepehr Soleymani、Rezvan Zabihollahi、Mohammad R. Aghasadeghi、Mehdi Sadat、Lotfollah Saghaie、Hamid R. Memarian、Afshin Fassihi

  DOI：10.1002/cbdv.201700502

  日期：2018.4

  A series of tetrahydropyrimidine derivatives (2a - 2l) were designed, synthesized, and screened for anti-HIV-1 properties based on the structures of HIV-1 gp41 binding site inhibitors, NB-2 and NB-64. A computational study was performed to predict the pharmacodynamics, pharmacokinetics, and drug-likeness features of the studied molecules. Docking studies revealed that the carboxylic acid group in the

  根据HIV-1 gp41结合位点抑制剂NB-2和NB-64的结构，设计，合成了一系列四氢嘧啶衍生物（2a-2l），并筛选了抗HIV-1特性。进行了一项计算研究，以预测所研究分子的药效动力学，药代动力学和类药物特征。对接研究表明，分子中的羧酸基与Lys574或Arg579形成盐桥。所合成化合物的理化性质（例如分子量，氢键供体的数目，氢键受体的数目和可旋转键的数目）证实并显示出这些化合物在李宾斯基五定律设定的范围内。在四氢嘧啶环的C（4）位置具有4-氯苯基取代基和4-甲基苯基的化合物2e和2k是最有效的化合物之一。这表明这些化合物可作为开发新型小分子HIV-1抑制剂的先导。
• Synthesis of fused dihydro-pyrimido[4,3-d]coumarins using Biginelli multicomponent reaction as key step
  作者：Mihaela Matache、Cristian Dobrota、Niculina D. Bogdan、Ioana Dumitru、Lavinia L. Ruta、Codruta C. Paraschivescu、Ileana C. Farcasanu、Ion Baciu、Daniel P. Funeriu

  DOI：10.1016/j.tet.2009.05.088

  日期：2009.8

  A new efficient approach for the synthesis of functionalized dihydro-pyrimido[4,3-d]coumarins is described. Use of benzyl- or tert-butyl acetoacetate and various salicyl aldehydes in typical Biginelli multicomponent reactions provides esters that can be easily deprotected to yield the corresponding hydroxy acids. Annelation of the latter leads to the target dihydro-pyrimido[4,3-d]coumarins. Formation of some unexpected oxo-bridged tetrahydro-pyrimidines is also described. Spectral properties of the synthesized dihydro-pyrimido[4,3-d]coumarins indicate the necessity to revisit some compounds previously reported as products of direct one-pot Biginelli condensation involving 4-hydroxycoumarin as dicarbonyl component. (C) 2009 Elsevier Ltd. All rights reserved.