pyridine-2-carboxylic acid (4,4-diphenylpropyl)amide

• 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: pyridine-2-carboxylic acid (4,4-diphenylpropyl)amide
• 英文别名: Pyridine-2-carboxylic acid (3,3-diphenyl-propyl)-amide；Pyridine-2-carboxylic Acid(4,4-Diphenyl-propyl)-amide；N-(3,3-diphenylpropyl)pyridine-2-carboxamide
• 化学式: C₂₁H₂₀N₂O
• 分子量: 316.403
• InChiKey: JLODJWGIRDCEPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  pyridine-2-carboxylic acid (4,4-diphenylpropyl)amide 、 4-乙炔基苯甲酸甲酯 、 Langlois reagent 在 copper acetylacetonate 、 过氧化苯甲酸叔丁酯 作用下， 以 乙腈 为溶剂， 以67 %的产率得到
  参考文献：
  名称：

  铜催化配位基团辅助的炔烃 1,2-二官能化三氟甲基酰胺化反应

  摘要：

  炔烃的自由基 1,2-双官能化反应已发展成为制备多取代亚烷基的通用方法。然而，尽管生成的烯胺在天然分子、生物活性和药物化合物中普遍存在，但仍缺乏进行碳胺化的强有力的催化策略。在此，我们表明，明智地安装在胺上的二齿配位基团可以作为实现炔烃自由基三氟甲基酰胺化的有效工具。该策略表现出广泛的底物范围和良好的官能团兼容性，适合天然化合物和生物学相关基序的后期功能化，从而可以直接合成大型 CF 3文库含有烯酰胺的高价值药效团，只需一步即可从易于获得的酰胺、朗格卢瓦试剂和炔烃中获得。目前的方法还可以成功扩展到炔烃的二氟甲基酰胺化。此外，还进行了各种机理实验，如竞争实验、H/D同位素交换实验、自由基陷阱实验、哈米特研究和动力学研究，以更好地理解反应机理。

  DOI：

  10.1021/acscatal.3c02662
• 作为产物：
  描述：

  2-吡啶甲酸 、 3,3-二苯基丙胺 在 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以11%的产率得到pyridine-2-carboxylic acid (4,4-diphenylpropyl)amide
  参考文献：
  名称：

  Structure-Based Optimization of Arylamides as Inhibitors of Soluble Epoxide Hydrolase

  摘要：

  Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of all effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection, The screen identified N-(3,3-diphenylpropyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.

  DOI：

  10.1021/jm9005302

文献信息

• Coordinating activation strategy enables 1,2-alkylamidation of alkynes
  作者：Jing Ren、Junhua Xu、Xiangxiang Kong、Jinlong Li、Kaizhi Li

  DOI：10.1039/d3sc03786j

  日期：——

  The radical 1,2-difunctional alkylamidation of alkynes has been developed with the help of a bidentate coordinating group for the synthesis of β-alkylated enamides.

  在双齿配位基团的帮助下，开发了炔烃的 1,2-二官能团烷基酰胺化作用，用于合成 β-烷基化烯酰胺。
• Structure-Based Optimization of Arylamides as Inhibitors of Soluble Epoxide Hydrolase
  作者：Anne B. Eldrup、Fariba Soleymanzadeh、Steven J. Taylor、Ingo Muegge、Neil A. Farrow、David Joseph、Keith McKellop、Chuk C. Man、Alison Kukulka、Stéphane De Lombaert

  DOI：10.1021/jm9005302

  日期：2009.10.8

  Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of all effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection, The screen identified N-(3,3-diphenylpropyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.
• Copper-Catalyzed 1,2-Difunctionalization Trifluoromethylamidation of Alkynes Assisted by a Coordinating Group
  作者：Jing Ren、Kaiyun Liu、Ning Wang、Xiangxiang Kong、Jinlong Li、Kaizhi Li

  DOI：10.1021/acscatal.3c02662

  日期：2023.8.18

  amenable for late-stage functionalization of natural compounds and biologically relevant motifs, allowing a straightforward synthesis of a large library of CF3-containing enamides, the high-value pharmacophores, in a single step from readily accessible amides, Langlois’ reagent, and alkynes. The current methodology can also be successfully extended to difluoromethylamidation of alkynes. Additionally

  炔烃的自由基 1,2-双官能化反应已发展成为制备多取代亚烷基的通用方法。然而，尽管生成的烯胺在天然分子、生物活性和药物化合物中普遍存在，但仍缺乏进行碳胺化的强有力的催化策略。在此，我们表明，明智地安装在胺上的二齿配位基团可以作为实现炔烃自由基三氟甲基酰胺化的有效工具。该策略表现出广泛的底物范围和良好的官能团兼容性，适合天然化合物和生物学相关基序的后期功能化，从而可以直接合成大型 CF 3文库含有烯酰胺的高价值药效团，只需一步即可从易于获得的酰胺、朗格卢瓦试剂和炔烃中获得。目前的方法还可以成功扩展到炔烃的二氟甲基酰胺化。此外，还进行了各种机理实验，如竞争实验、H/D同位素交换实验、自由基陷阱实验、哈米特研究和动力学研究，以更好地理解反应机理。