4-phenylamino-1H-pyridin-2-one | 74990-54-8

• 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: 4-phenylamino-1H-pyridin-2-one
• 英文别名: 4-anilino-2-oxo-1,2-dihydropyridine；4-(phenylamino)pyridin-2(1H)-one；4-anilino-1H-pyridin-2-one
• CAS: 74990-54-8
• 化学式: C₁₁H₁₀N₂O
• 分子量: 186.213
• InChiKey: WFJNDJGLKSAHNS-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230 °C(Solv: ethanol (64-17-5))
• 沸点：
  385.0±42.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-phenylamino-1H-pyridin-2-one 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1-chloro-benzo[b][1,6]naphthyridine
  参考文献：
  名称：

  吡啶并茂新合成[4,3- b ]喹诺酮类药物替代品1

  摘要：

  关于新合成的吡啶并[4,3- b ]喹诺酮类化合物的替代品，它取代了合法的三色混合物。décritune nouvellesynthèsede pyrido [4,3- b ]quinoléines多样化替代了leur sommet 1 qui comporte seulement troisétapes。Vinsmeir-Haack反应条件的羟基二芳基氨基-4吡啶类化合物，由oxo-1二氢-1，2-吡啶基[4,3- b ]喹啉制成；氯代吡啶类化合物随同氯代-1吡啶基[4,3- b ]喹啉类化合物的替代品被同等胺类取代。

  DOI：

  10.1002/jhet.5570170208
• 作为产物：
  描述：

  2,4-二氯吡啶 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 potassium hydride 、 sodium t-butanolate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 反应 21.25h， 生成 4-phenylamino-1H-pyridin-2-one
  参考文献：
  名称：

  Development of peptidomimetic boronates as proteasome inhibitors

  摘要：

  Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (beta 5), trypsin-like (beta 2) and caspase-like (beta 1). Most important for the development of effective antitumor agents is the inhibition of the beta 5 subunits. In this context, the dipeptide boronate bortezomib (Velcade (R)) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide boronates (1-3) structurally related to bortezomib. The synthesized compounds showed a promising inhibitory profile by blocking primarily the chymotrypsin-like activity of the proteasome with K-i values in submicromolar/micromolar range. These compounds also resulted quite selective since no significant inhibition was recorded in the test against bovine pancreatic alpha-chymotrypsin. The obtained results were rationalized by means of docking experiments based on a model of the crystal structure of bortezomib bound to the yeast 20S proteasome providing essential insights for further optimization of this class of inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.032

文献信息

• Development of Novel Selective Peptidomimetics Containing a Boronic Acid Moiety, Targeting the 20S Proteasome as Anticancer Agents
  作者：Kety Scarbaci、Valeria Troiano、Roberta Ettari、Andrea Pinto、Nicola Micale、Carmen Di Giovanni、Carmen Cerchia、Tanja Schirmeister、Ettore Novellino、Antonio Lavecchia、Maria Zappalà、Silvana Grasso

  DOI：10.1002/cmdc.201402075

  日期：2014.5.28

  This paper describes the design, synthesis, and biological evaluation of peptidomimetic boronates as inhibitors of the 20S proteasome, a validated target in the treatment of multiple myeloma. The synthesized compounds showed a good inhibitory profile against the ChT‐L activity of 20S proteasome. Compounds bearing a β‐alanine residue at the P2 position were the most active, that is, 3‐ethylphenylamino

  本文描述了拟肽样硼酸盐作为20S蛋白酶体抑制剂的设计，合成和生物学评估，20S蛋白酶体是治疗多发性骨髓瘤的有效靶点。合成的化合物对20S蛋白酶体的ChT-L活性表现出良好的抑制作用。在P2位置带有β-丙氨酸残基的化合物活性最高，即3-乙基苯氨基和4-甲氧基苯基氨基（R）-1- 3- [4-（取代）-2--2-氧代吡啶-1（2 H）-基]丙酰胺基} -3-甲基丁基硼酸（分别为3 c和3 d），这些衍生物的抑制常数（K i）为17和20 n M， 分别。此外，它们共抑制交谷氨酰肽水解酶的活性（图3c，ķ我= 2.57μ中号; 3 d，ķ我= 3.81μ中号）。没有记录到对牛胰α-胰凝乳蛋白酶的抑制作用，因此证实了对靶酶的选择性。3 c和相关抑制剂对接研究到酵母蛋白酶体揭示了特异性的结构基础。在美国国家癌症研究所进行了针对60种人类肿瘤细胞系的生长抑制作用评估。在选定的化合物中，3 c显示出50％的生长抑制（GI
• Reactions of aminoguanidine and guanidine with 3- and 5-formyl-4-arylaminopyridones
  作者：M. I. Medvedeva、N. Z. Tugusheva、L. M. Alekseeva、M. A. Kalinkina、V. A. Parshin、V. V. Chernyshev、V. I. Levina、N. B. Grigor’ev、A. S. Shashkov、V. G. Granik

  DOI：10.1007/s11172-010-0385-8

  日期：2010.12

  investigate their biological activity as putative NO donors. The reaction of 5- и 3-formylpyridones with diguanidinium carbonate was studied. The formation of stable complexes of 4-arylamino-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitriles with aminoguanidine and guanidine was discovered. Amidinohydrazones obtained possess antiinflammatory, antidiabetic, and antihypertensive activities.

  脒腙是通过 4-arylamino-2-oxo-5-formyl-1,2-dihydropyridine-3-carbonitriles 和 4-arylamino-2-oxo-1,2-dihydropyridine-3-carbaldehydes 与氨基胍碳酸盐与目的是研究它们作为推定的 NO 供体的生物活性。研究了 5- 和 3-甲酰基吡啶酮与碳酸二胍的反应。发现了 4-芳基氨基-5-甲酰基-2-氧代-1,2-二氢吡啶-3-甲腈与氨基胍和胍的稳定复合物的形成。获得的脒腙具有抗炎、抗糖尿病和抗高血压活性。
• RIVALLE C.; BISAGNI E., J. HETEROCYCL. CHEM., 1980, 17, NO 2, 245-248
  作者：RIVALLE C.、 BISAGNI E.

  DOI：——

  日期：——
• Development of peptidomimetic boronates as proteasome inhibitors
  作者：Nicola Micale、Roberta Ettari、Antonio Lavecchia、Carmen Di Giovanni、Kety Scarbaci、Valeria Troiano、Silvana Grasso、Ettore Novellino、Tanja Schirmeister、Maria Zappalà

  DOI：10.1016/j.ejmech.2013.03.032

  日期：2013.6

  Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (beta 5), trypsin-like (beta 2) and caspase-like (beta 1). Most important for the development of effective antitumor agents is the inhibition of the beta 5 subunits. In this context, the dipeptide boronate bortezomib (Velcade (R)) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide boronates (1-3) structurally related to bortezomib. The synthesized compounds showed a promising inhibitory profile by blocking primarily the chymotrypsin-like activity of the proteasome with K-i values in submicromolar/micromolar range. These compounds also resulted quite selective since no significant inhibition was recorded in the test against bovine pancreatic alpha-chymotrypsin. The obtained results were rationalized by means of docking experiments based on a model of the crystal structure of bortezomib bound to the yeast 20S proteasome providing essential insights for further optimization of this class of inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Nouvelle synthèse des pyrido[4,3-<i>b</i>]quinoléines substituées sur leur sommet 1
  作者：Christian Rivalle、Emile Bisagni

  DOI：10.1002/jhet.5570170208

  日期：1980.3

  diversement substituées sur leur sommet 1 qui comporte seulement trois étapes. Ainsi, les hydroxy-2 arylamino-4 pyridines sont transformées dans les conditions de la réaction de Vilsmeir-Haack en donnant directement les oxo-1 dihydro-1,2 pyrido[4,3-b]quinoléines; la chloration de ces dernières engendre ensuite les chloro-1 pyrido[4,3-b]quinoléines qui sont aisément substituées par des amines variées.

  关于新合成的吡啶并[4,3- b ]喹诺酮类化合物的替代品，它取代了合法的三色混合物。décritune nouvellesynthèsede pyrido [4,3- b ]quinoléines多样化替代了leur sommet 1 qui comporte seulement troisétapes。Vinsmeir-Haack反应条件的羟基二芳基氨基-4吡啶类化合物，由oxo-1二氢-1，2-吡啶基[4,3- b ]喹啉制成；氯代吡啶类化合物随同氯代-1吡啶基[4,3- b ]喹啉类化合物的替代品被同等胺类取代。