1-(4-aminobenzyl)-5-(trifluoromethyl)pyridin-2(1H)-one | 1256782-84-9

• 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: 1-(4-aminobenzyl)-5-(trifluoromethyl)pyridin-2(1H)-one
• 英文别名: 1-[(4-Aminophenyl)methyl]-5-(trifluoromethyl)pyridin-2-one
• CAS: 1256782-84-9
• 化学式: C₁₃H₁₁F₃N₂O
• 分子量: 268.238
• InChiKey: OSBVVTNMGMJFNM-UHFFFAOYSA-N

物化性质

• 沸点：
  404.9±45.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-aminobenzyl)-5-(trifluoromethyl)pyridin-2(1H)-one 在 sodium iodide 氯化亚砜 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 正丁醇 为溶剂， 反应 52.0h， 生成 1-(4-(2-(2-hydroxyethoxy)ethylamino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one
  参考文献：
  名称：

  PREPARATION OF 1-(SUBSTITUTED BENZYL)-5-TRIFLUOROMETHYL-2(1H)PYRIDONE COMPOUNDS AND SALTS THEREOF AND THEIR APPLICATIONS

  摘要：

  揭示了1-(取代苄基)-5-三氟甲基-2(1H)吡啶酮化合物及其药用可接受盐。还公开了这些化合物及其盐的制备方法，以及用于制备治疗纤维化药物的用途。从三氟甲基吡啶酮作为起始物获得了新的吡啶化合物及其盐。

  公开号：

  US20120129859A1
• 作为产物：
  描述：

  1-(氯甲基)-4-硝基苯 在 盐酸 、 铁粉 、 potassium carbonate 作用下， 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 4.0h， 生成 1-(4-aminobenzyl)-5-(trifluoromethyl)pyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of 1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one, an orally active multi-target agent for the treatment of diabetic nephropathy

  摘要：

  Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC50 of 90 mu M in NIH3T3 cell lines, t(1/2) of 4.89 +/- 1.33 h in male rats and LD50 > 2000 mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.07.001

文献信息

• Design, Synthesis and Antifibrotic Activities of Carbohydrate- Modified 1-(Substituted aryl)-5-trifluoromethyl-2(1H) Pyridones
  作者：Qinghua Lou、Xiangbao Meng、Zhiqi Lao、Lingling Xuan、Jinye Bai、Qi Hou、Gaoyun Hu、Renna Luo、Lijian Tao、Zhongjun Li

  DOI：10.3390/molecules17010884

  日期：——

  Pirfenidone, a pyridone compound, is an effective and novel antifibrotic agent. In this article, we describe the design, synthesis and activity evaluation of novel antifibrotic agents, 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones modified with carbohydrate. Most of the title compounds exhibited comparable or better inhibitory activity than fluorofenidone. Notably, compound 19a demonstrated the highest cell-based inhibitory activity against NIH 3T3 (IC50 = 0.17 mM).

  吡非尼酮（Pirfenidone），一种吡啶酮化合物，是一种有效且新颖的抗纤维化药物。本文中，我们描述了新型抗纤维化药物的设计、合成及活性评估，这些药物为1-（取代芳基）-5-三氟甲基-2（1H）吡啶酮，经碳水化合物修饰。标题化合物大多展现出与氟非尼酮相当或更优的抑制活性。值得注意的是，化合物19a对NIH 3T3细胞的抑制活性最高（IC50 = 0.17 mM）。
• Synthesis and structure–activity relationship of 5-substituent-2(1H)-pyridone derivatives as anti-fibrosis agents
  作者：Jun Chen、Miao-Miao Lu、Bin Liu、Zhuo Chen、Qian-Bin Li、Li-Jian Tao、Gao-Yun Hu

  DOI：10.1016/j.bmcl.2012.01.073

  日期：2012.3

  Pyridone compounds, such as pirfenidone (PFD) and fluorofenidone (AKF-PD), are multi-target anti-fibrotic agents. Using PFD and AKF-PD as the leading compounds, two series of novel (5-substituent)-2(1H)-pyridone compounds were synthesized with the purpose of maintaining multi-targeting property and overcoming the drawbacks of fast metabolism. These derivatives demonstrated good proliferation inhibiting

  吡啶酮化合物（例如吡非尼酮（PFD）和氟苯尼酮（AKF-PD））是多靶点抗纤维化药物。以PFD和AKF-PD为主导化合物，合成了两种新型的（5-取代基）-2（1 H）-吡啶酮化合物，以维持多靶点性质并克服快速代谢的缺点。这些衍生物通过以AKF-PD作为阳性对照的MTT分析显示出对NIH3T3细胞的良好增殖抑制活性。化合物5b具有很高的抗纤维化作用，IC 50为0.08 mmol / L，约为AKF-PD的34倍。还讨论了吡啶酮衍生物作为抗纤维化剂的SAR。
• 抗肾纤维化药物1-（取代苄基）-5-三氟甲基-2 (1H)-吡啶酮盐酸盐的合成方法
  申请人：广州南新制药有限公司

  公开号：CN107652228B

  公开（公告）日：2020-04-14

  本发明涉及一种抗肾纤维化药物1‑（（4‑（4‑甲基哌嗪‑1‑基）丙基）氨基）苄基‑5‑三氟甲基‑2（1H）‑酮盐酸盐（ZHC‑116盐酸盐）的合成方法。本发明以2‑氯‑5‑三氟甲基吡啶（商业购得）为原料，经过9步合成步骤制备1‑（（4‑（4‑甲基哌嗪‑1‑基）丙基）氨基）苄基‑5‑三氟甲基‑2（1H）‑酮。相比现有文献报道的方法，本发明的方法有效、实用，总合成收率有所提高，适合工业规模化生产。
• Synthesis and evaluation of new pirfenidone derivatives as anti-fibrosis agents
  作者：Chenxi Gu、Wei Li、Qing Ju、Han Yao、Lisheng Yang、Baijiao An、Wenhao Hu、Xingshu Li

  DOI：10.1039/d2ra00990k

  日期：——

  Two series of new pirfenidone derivatives, in which phenyl groups or benzyl groups are attached to the nitrogen atom of the pyridin-2(1H)-one moiety were synthesized and evaluated as anti-fibrosis agents. Among them, compound 5d, with a (S)-2-(dimethylamino) propanamido group in the R2 position (series 1) exhibited 10 times the anti-fibrosis activity (IC50: 0.245 mM) of pirfenidone (IC50: 2.75 mM)

  合成了两个系列的新吡非尼酮衍生物，其中苯基或苄基连接到 pyridin-2(1 H )-one 部分的氮原子上，并作为抗纤维化剂进行了评估。其中，在R 2位具有( S )-2-(二甲氨基)丙酰胺基的化合物5d (系列1)表现出10倍于吡非尼酮(IC 50 : 2.75 )的抗纤维化活性(IC 50 : 0.245 mM)毫米）。化合物9d (系列 2)对人成纤维细胞系 HFL1的 IC 50为 0.035 mM。还研究了最佳化合物抑制纤维化的机制。
• 1-(SUBSTITUTED BENZYL)-5-TRIFLUOROMETHYL-2-(1H) PYRIDONE COMPOUNDS AND THEIR SALTS, THEIR PREPARATION METHODS AND USE THEREOF
  申请人：Central South University

  公开号：EP2474533A1

  公开（公告）日：2012-07-11

  1-(substituted benzyl)-5-trifluoromethyl-2(1H)pyridone compounds and their pharmaceutical acceptable salts are disclosed. The preparation methods of the compounds and their salts and the use of the same for preparing the medicaments for treating fibrosis are also disclosed. New pyridine compounds and their salts are obtained from trifluoromethyl pyridone as starting material.

  本发明公开了 1-(取代苄基)-5-三氟甲基-2(1H)吡啶酮化合物及其药用盐。此外，还公开了这些化合物及其盐的制备方法和用于制备治疗纤维化药物的用途。以三氟甲基吡啶酮为起始原料，可获得新的吡啶化合物及其盐。