4-(Piperidin-1-yl)-1,2-dihydropyridin-2-one | 1006052-99-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(Piperidin-1-yl)-1,2-dihydropyridin-2-one
• 英文别名: 4-piperidin-1-yl-1H-pyridin-2-one
• CAS: 1006052-99-8
• 化学式: C₁₀H₁₄N₂O
• 分子量: 178.234
• InChiKey: PKZQVYKRGZALPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(Piperidin-1-yl)-1,2-dihydropyridin-2-one 在 盐酸 、 异丁基硼酸 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 (R)-1-{3-[2-oxo-4-(piperidin-1-yl)pyridin-1(2H)-yl]propanamido}-3-methylbutylboronic acid
  参考文献：
  名称：

  以20S蛋白酶体为抗癌剂的新型含硼酸选择性肽模拟物的开发

  摘要：

  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

  DOI：

  10.1002/cmdc.201402075
• 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-(Piperidin-1-yl)-1,2-dihydropyridin-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 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.
• 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