1-(4-fluorophenyl)-2-(methylamino)ethanone hydrochloride | 125185-76-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluorophenyl)-2-(methylamino)ethanone hydrochloride
• 英文别名: 1-(4-Fluorophenyl)-2-methylamino-1-oxo-ethane hydrochloride；1-(4-fluorophenyl)-2-(methylamino)ethanone;hydrochloride
• CAS: 125185-76-4
• 化学式: C₉H₁₀FNO*ClH
• 分子量: 203.644
• InChiKey: HCDZHHQWZNOVLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.65
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  29.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-2-(methylamino)ethanone hydrochloride 、 sodium thiocyanide 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以88%的产率得到4-(4-fluorophenyl)-1-methyl-1H-imidazole-2-thiol
  参考文献：
  名称：

  Synthesis and Metabolic Studies of Host-Directed Inhibitors for Antiviral Therapy

  摘要：

  Targeting host cell factors required for virus replication provides an alternative to targeting pathogen components and represents a promising approach to develop broad-spectrum antiviral therapeutics. High-throughput screening (HTS) identified two classes of inhibitors (2 and 3) with broad-spectrum antiviral activity against ortho- and paramyxoviruses including influenza A virus (IAV), measles virus (MeV), respiratory syncytial virus (RSV), and human parainfluenza virus type 3 (HPIV3). Hit-to-lead optimization delivered inhibitor 28a, with EC50 values of 0.88 and 0.81 mu M against IAV strain WSN and MeV strain Edmonston, respectively. It was also found that compound 28a delivers good stability in human liver S9 fractions with a half-life of 165 min. These data establish 28a as a promising lead for antiviral therapy through a host-directed mechanism.

  DOI：

  10.1021/ml400166b
• 作为产物：
  描述：

  2-(Benzyl-methylamino)-1-(4-fluorophenyl)-1-oxo-ethane hydrochloride 在 钯 氮 、 氢气 、 水 作用下， 以 溶剂黄146 为溶剂， 生成 1-(4-fluorophenyl)-2-(methylamino)ethanone hydrochloride
  参考文献：
  名称：

  Substituted imidazolinones and imidazolinethiones

  摘要：

  式子为 ##STR1## 的HMG-CoA还原酶抑制化合物，其中R.sup.1是可选择取代的烷基或环烷基基团，R.sup.2是可选择取代的芳基或杂环芳基基团，R.sup.3是氢或有机基团，B为O或S，X为--CH.sub.2 --CH.sub.2或--CH.dbd.CH--，A为##STR2## R.sup.6是氢或烷基，R.sup.7是氢、烷基、芳基烷基、芳基或阳离子。

  公开号：

  US04973598A1

文献信息

• Regiospecific and Highly Flexible Synthesis of 1,4,5-Trisubstituted 2-Sulfanylimidazoles from Structurally Diverse Ethanone Precursors
  作者：Stefan Laufer、Dominik Hauser、Andy Liedtke

  DOI：10.1055/s-2007-1000852

  日期：2008.1

  Imidazoles represent important bioactive scaffolds in medicinal chemistry. More than 2,500 structures are listed in drug discovery databases and over 3,000 patents have been claimed for imidazole-based structures. Recent imidazole pharmacophores have targeted various MAP kinases. p38 Mitogen-activated protein (MAP) kinase plays a central role in the signaling network responsible for the upregulation of proinflammatory cytokines like IL-1β and TNFα and offers, therefore, a valid target for small molecule anti-inflammatory drugs. 2-Sulfanylimidazole derivatives offer some advantages over prototype inhibitors (SB203580), e.g. lower cytochrom P450 interactions and better kinetic properties. We report here three novel regioselective and, at the same time, highly flexible synthetic approaches towards 1,4,5-trisubstituted 2-sulfanylimidazoles starting from different ethanone regioisomers allowing maximum variability of all substituents introduced. As a result, a variety of selective and highly potent p38 MAPK inhibitors were prepared and selected for further preclinical development. Synthesis of structurally diverse inhibitor candidates, p38 inhibition data, and selectivity profiling of some selected compounds are specified. Furthermore, the benefits of the useful, brief synthetic sequences are outlined and contrasted with already published multistep routes.

  咪唑类是药物化学中重要的生物活性骨架。药物发现数据库中列出了超过2,500种结构，并且已有超过3,000项专利针对咪唑类结构提出申请。最近的咪唑类药效团主要针对各种MAP激酶。p38丝裂原活化蛋白（MAP）激酶在信号网络中起着核心作用，该网络负责上调如IL-1β和TNFα等促炎细胞因子，因此，它为小分子抗炎药物提供了有效的靶点。2-巯基咪唑衍生物相较于原型抑制剂（如SB203580）具有一些优势，例如较低的细胞色素P450相互作用和更好的动力学特性。我们在此报告了三种新颖的区域选择性且高度灵活的合成方法，这些方法从不同的乙酮区域异构体出发，实现了对所有引入取代基的最大可变性，从而合成了1,4,5-三取代的2-巯基咪唑。由此，制备并筛选出一系列选择性强且高效的p38 MAPK抑制剂，用于进一步的临床前开发。详细描述了结构多样化的抑制剂候选物的合成、p38抑制数据以及部分精选化合物的选择性分析。此外，还概述了简短合成序列的优点，并与已发表的多步骤路线进行了对比。
• COMPOUNDS USEFUL AS MODULATORS OF TRPM8
  申请人：SENOMYX, INC.

  公开号：US20150376136A1

  公开（公告）日：2015-12-31

  The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.

  本发明包括作为TRPM8调节剂有用的化合物，例如式(Ia)、(Ib)和(Ic)的化合物，以及其亚属和种类；含有这些化合物的个人产品；以及利用这些化合物和个人产品，特别是利用增加或诱导化学感觉，如凉爽或冷感觉。
• Compounds useful as modulators of TRPM8
  申请人：Firmenich Incorporated

  公开号：US10421727B2

  公开（公告）日：2019-09-24

  The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.

  本发明包括可用作 TRPM8 调节剂的化合物，如式（Ia）、（Ib）和（Ic）化合物及其亚属和种；含有这些化合物的个人用品；以及这些化合物和个人用品的用途，特别是增加或诱导化学麻醉感觉的用途，如冷却或冷感。
• FEY, PETER;ANGERBAUER, ROLF;HUBSCH, WALTER;BISCHOFF, HILMAR;PETZINNA, DIE+
  作者：FEY, PETER、ANGERBAUER, ROLF、HUBSCH, WALTER、BISCHOFF, HILMAR、PETZINNA, DIE+

  DOI：——

  日期：——
• FIVE-MEMBERED HETEROCYLIC COMPOUNDS USEFUL AS MODULATORS OF TRPM8
  申请人：Firmenich Incorporated

  公开号：EP3461816B1

  公开（公告）日：2021-03-24