2-methoxy-6-oxo-5-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile | 148055-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-methoxy-6-oxo-5-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile
• 英文别名: 2-methoxy-5-phenyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitrile；6-methoxy-2-oxo-3-phenyl-3,4-dihydro-1H-pyridine-5-carbonitrile
• CAS: 148055-95-2
• 化学式: C₁₃H₁₂N₂O₂
• 分子量: 228.25
• InChiKey: HJMKPRCBJJCQNZ-UHFFFAOYSA-N

物化性质

• 沸点：
  494.7±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methoxy-6-oxo-5-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile 在 sodium hydride 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 3-amino-7-methyl-2,5-diphenyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
  参考文献：
  名称：

  Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c01941
• 作为产物：
  描述：

  苯乙酸甲酯 在 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2-methoxy-6-oxo-5-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile
  参考文献：
  名称：

  Investigating molecular dynamics-guided lead optimization of EGFR inhibitors

  摘要：

  The epidermal growth factor receptor (EGFR) is part of an extended family of proteins that together control aspects of cell growth and development, and thus a validated target for drug discovery. We explore in this work the suitability of a molecular dynamics-based end-point binding free energy protocol to estimate the relative affinities of a virtual combinatorial library designed around the EGFR model inhibitor 6{1} as a tool to guide chemical synthesis toward the most promising compounds. To investigate the validity of this approach, selected analogs including some with better and worse predicted affinities relative to 6{1} were synthesized, and their biological activity determined. To understand the binding determinants of the different analogs, hydrogen bonding and van der Waals contributions, and water molecule bridging in the EGFR-analog complexes were analyzed. The experimental validation was in good qualitative agreement with our theoretical calculations, while also a 6-dibromophenyl-substituted compound with enhanced inhibitory effect on EGFR compared to the reference ligand was obtained. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.046

文献信息

• C4–C5 fused pyrazol-3-amines: when the degree of unsaturation and electronic characteristics of the fused ring controls regioselectivity in Ullmann and acylation reactions
  作者：Elisabeth Bou-Petit、Arnau Plans、Nieves Rodríguez-Picazo、Antoni Torres-Coll、Cristina Puigjaner、Mercè Font-Bardia、Jordi Teixidó、Santiago Ramon y Cajal、Roger Estrada-Tejedor、José I. Borrell

  DOI：10.1039/d0ob00796j

  日期：——

  number of compounds with a wide range of biological activities and, in many cases, the heterocycle is C4–C5 fused to a second ring. Among the different reactions used for the decoration of the pyrazole ring, Ullmann and acylation have been widely applied. However, there is some confusion in the literature regarding the regioselectivity of such reactions (substitution at N1 or N2 of the pyrazole ring) and

  吡唑-3-胺是存在于许多具有广泛生物活性的化合物中的支架，在许多情况下，杂环是C4–C5与第二个环稠合。在用于装饰吡唑环的不同反应中，Ullmann和酰化已得到广泛应用。然而，关于此类反应的区域选择性（吡唑环的N1或N2取代）的文献存在混淆，并且迄今尚未建立预测规则。作为我们对3-氨基-吡唑并[3,4- b ]吡啶酮的研究13，我们研究了在不同的C4–C5稠合的吡唑-3-胺中此类反应的区域选择性。根据经验，Ullmann和酰化反应主要发生在最稳定的初始互变异构体（1H-或2H-吡唑）的吡唑环的NH和非质子化氮原子上。通过使用DFT计算进行预测。
• Design, synthesis and biological evaluation of pyrido[2,3-d]pyrimidin-7-(8H)-ones as HCV inhibitors
  作者：Marta Camarasa、Raimon Puig de la Bellacasa、Àlex L. González、Raül Ondoño、Roger Estrada、Sandra Franco、Roger Badia、José Esté、Miguel Ángel Martínez、Jordi Teixidó、Bonaventura Clotet、José I. Borrell

  DOI：10.1016/j.ejmech.2016.03.055

  日期：2016.6

  design and selection of a combinatorial library of pyrido[2,3-d]pyrimidin-7(8H)-ones (4) has allowed the synthesis of 121 compounds, using known and new synthetic methodologies, and the evaluation of the inhibitory activity against hepatitis C virus (HCV) genotype 1b replicon. Among these compounds, 214,10} and 242,10} presented very high activities [EC50 = 0.027 μM (CC50 = 5.3 μM) and EC50 = 0.034 μM

  吡啶并[2,3 - d ]嘧啶-7（8 H）-ones（4）的组合文库的设计和选择已允许使用已知的和新的合成方法合成121种化合物，并对其抑制性进行评估抗丙型肝炎病毒（HCV）基因型1b复制子的活性。在这些化合物中，21 4,10 }和24 2,10 }表现出非常高的活性[分别为EC 50  = 0.027μM（CC 50  = 5.3μM）和EC 50  = 0.034μM（CC 50  = 13.5μM）]和高选择性指数196和397。这些值类似于EC 50索非布韦（2）（0.048μM ）使用相似的方法学方法和相同的病毒亚型报道。21 4,10 }和24 2,10 }是通过比sofosbuvir短的合成路线而获得的，而24 2,10 }是非手性的，与sofosbuvir具有4个立体生成中心相反。计算机研究表明21 4,10 }和24 2,10 }通过变构位点结合抑制NS5B聚合酶。
• Structure of 2-cyano-4-phenyl-glutarimide studied by X-ray diffraction, vibrational spectroscopy and ab initio methods
  作者：Dariusz C. Bieńko、Danuta Michalska、José I. Borrell、Jordi Teixidó、Josep L. Matallana、Angel Alvarez-Larena、Joan F. Piniella

  DOI：10.1016/s0022-2860(98)00382-2

  日期：1998.11

  structure of 2-cyano-4-phenylglutarimide (3c) has been studied by single-crystal X-ray diffraction, infrared and Raman spectroscopies and ab initio methods. The crystals are monoclinic, space group P212121, with a=5.970(2), b=8.569(1), c=19.982(3) A and z=4. The X-ray diffraction study showed the presence of only one diastereomer of 3c, the relative configuration of which could be either SC3RC5 or RC3SC5

  摘要 2-氰基-4-苯基戊二酰亚胺(3c) 的结构已通过单晶X 射线衍射、红外和拉曼光谱以及从头算方法进行了研究。晶体为单斜晶系，空间群 P212121，a=5.970(2), b=8.569(1), c=19.982(3) A 和 z=4。X 射线衍射研究表明仅存在 3c 的一种非对映异构体，其相对构型可以是 SC3RC5 或 RC3SC5，氰基和苯基都位于赤道位置。晶体堆积由弱分子间 N-H⋯O、C-H⋯O 和 C-H⋯N 氢键网络稳定。在 HF/D95V** ab initio 水平计算的分子结构与在晶体中观察到的结构非常一致。报告了 2-cyano-4-phenylglutarimide 的特征红外和拉曼带的分配。
• Victory, Pedro J.; Teixido, Jordi; Borrell, Jose I., Heterocycles, 1992, vol. 34, # 10, p. 1905 - 1916
  作者：Victory, Pedro J.、Teixido, Jordi、Borrell, Jose I.

  DOI：——

  日期：——
• Victory, Pedro; Busquets, Nuria; Borrell, Jose I., Heterocycles, 1995, vol. 41, # 10, p. 2173 - 2180
  作者：Victory, Pedro、Busquets, Nuria、Borrell, Jose I.、Teixido, Jordi、Alvaro, Carlos de、et al.

  DOI：——

  日期：——