4-氯-N-(2,6-二甲基苯基)-丁酰胺 | 77470-76-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氯-N-(2,6-二甲基苯基)-丁酰胺
• 英文名称: 4-chlorobutyro-2',6'-xylidide
• 英文别名: 4-chloro-N-(2,6-dimethylphenyl)butanamide
• CAS: 77470-76-9
• 化学式: C₁₂H₁₆ClNO
• mdl: MFCD00128387
• 分子量: 225.718
• InChiKey: BDSZSYFXLCPIKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  4-氯-N-(2,6-二甲基苯基)-丁酰胺 在 盐酸 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 生成 4-amino-N-(2,6-dimethylphenyl)butanamide
  参考文献：
  名称：

  New antiarrhythmic agents. 6. Quantitative structure-activity relationships of aminoxylidides

  摘要：

  The synthesis and pharmacological evaluation of primary and tertiary aminoxylidides with the amino group in the 2-7 position of the acyl chain are described. 2,6-Xylidine was acylated with haloacyl halides and converted to the target compounds by direct amination or by the Gabriel procedure. Alternatively, 2,6-xylidine was coupled with keto acids, and the ketoxylidides were converted to the amines by reductive amination. The target compounds were evaluated in mice both for antiarrhythmic efficacy against chloroform-induced tachycardia and for central nervous system toxicity. Experimentally determined values of partition coefficients and pKa values were used for quantitative structure-activity analyses. While the antiarrhythmic activity could be described as a function of log P alone, the CNS toxicity was best described as a function of both log P and pKa. The results suggest that antiarrhythmic potency can be increased by increasing lipophilicity, while the therapeutic index can be improved by increasing the pKa.

  DOI：

  10.1021/jm00139a007
• 作为产物：
  描述：

  5-chloropentano-2',6'-xylidide 在 sodium acetate 、 sodium iodide 作用下， 以 乙醇 、 水 、 溶剂黄146 为溶剂， 反应 51.5h， 生成 4-氯-N-(2,6-二甲基苯基)-丁酰胺
  参考文献：
  名称：

  New antiarrhythmic agents. 6. Quantitative structure-activity relationships of aminoxylidides

  摘要：

  The synthesis and pharmacological evaluation of primary and tertiary aminoxylidides with the amino group in the 2-7 position of the acyl chain are described. 2,6-Xylidine was acylated with haloacyl halides and converted to the target compounds by direct amination or by the Gabriel procedure. Alternatively, 2,6-xylidine was coupled with keto acids, and the ketoxylidides were converted to the amines by reductive amination. The target compounds were evaluated in mice both for antiarrhythmic efficacy against chloroform-induced tachycardia and for central nervous system toxicity. Experimentally determined values of partition coefficients and pKa values were used for quantitative structure-activity analyses. While the antiarrhythmic activity could be described as a function of log P alone, the CNS toxicity was best described as a function of both log P and pKa. The results suggest that antiarrhythmic potency can be increased by increasing lipophilicity, while the therapeutic index can be improved by increasing the pKa.

  DOI：

  10.1021/jm00139a007

文献信息

• Novel indole based hybrid oxadiazole scaffolds with <i>N</i>-(substituted-phenyl)butanamides: synthesis, lineweaver–burk plot evaluation and binding analysis of potent urease inhibitors
  作者：Majid Nazir、Muhammad Athar Abbasi、Aziz-ur-Rehman Aziz-ur-Rehman、Sabahat Zahra Siddiqui、Hussain Raza、Mubashir Hassan、Syed Adnan Ali Shah、Muhammad Shahid、Sung-Yum Seo

  DOI：10.1039/c8ra04987d

  日期：——

  In the study presented herein, 4-(1H-indol-3-yl)butanoic acid (1) was sequentially transformed in the first phase into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3) and 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4) as a nucleophile.

  在本研究中，4-(1H-吲哚-3-基)丁酸（1）在第一阶段依次转化为乙基4-(1H-吲哚-3-基)丁酸酯（2），4-(1H-吲哚-3-基)丁酸肼（3）和作为亲核试剂的5-[3-(1H-吲哚-3-基)丙基]-1,3,4-噁二唑-2-硫醇（4）。
• 2‐Aminothiazole‐Oxadiazole Bearing <i>N</i> ‐Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure‐Activity Relationship, and Binding Conformations
  作者：Hussain Raza、Abdul Rehman Sadiq Butt、Muhammad Athar Abbasi、Aziz‐ur‐Rehman、Sabahat Zahra Siddiqui、Mubashir Hassan、Syed Adnan Ali Shah、Song Ja Kim

  DOI：10.1002/cbdv.202201019

  日期：2023.2

  A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a–h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk

  通过收敛策略完成了新型双杂环N-芳基化丁酰胺的多步合成，并使用光谱技术证实了这些药用支架7a–h的结构。与所用标准相比，这些杂合分子的体外分析揭示了它们有效的酪氨酸酶抑制作用。通过 Lineweaver-Burk 图研究了动力学机制，该图显示7f通过形成酶-抑制剂复合物非竞争性地抑制酪氨酸酶。从该化合物的 Dixon 图计算出的抑制常数 K i为 0.025 μM。它们的结合构象是通过in silico确定的计算研究表明这些分子具有良好的结合能值 (kcal/mol)。因此，从目前的研究中可以预期，这些双杂环丁酰胺可能被探索为黑色素生成的必要治疗剂。
• Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: <i>De Novo</i> Molecular Generation Based on a Low Activity Lead Compound
  作者：Hong Cai、Wenchao Chen、Jing Jiang、Hao Wen、Xinyu Luo、Junjie Li、Liuxin Lu、Rui Zhao、Xinhua Ni、Yinyan Sun、Jiahui Wang、Zhen Li、Bin Ju、Xiaoying Jiang、Renren Bai

  DOI：10.1021/acs.jmedchem.4c00091

  日期：——

  Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces a fragment-by-fragment growth RL forward molecular generation and optimization strategy based on a low activity lead compound. This process integrates fragment growth-based reaction templates, while

  人工智能 (AI)从头分子生成是药物发现中非常有前途的策略，深度强化学习 (RL) 模型正在成为强大的工具。本研究介绍了基于低活性先导化合物的逐片段生长 RL 正向分子生成和优化策略。该过程集成了基于片段生长的反应模板，同时进行靶标对接和药物相似性预测。这种综合方法考虑了分子相似性、内部多样性、可合成性和有效性，从而提高了分子生成的质量和效率。最终生成并合成了一系列酪氨酸酶抑制剂。大多数化合物表现出比铅更好的活性，最佳候选化合物超越了曲酸的效果，并在斑马鱼模型中表现出显着的抗色素沉着活性。此外，代谢稳定性研究表明对肝脏代谢的敏感性。所提出的人工智能结构优化策略将在加速药物发现和提高传统效率方面发挥重要作用。
• TENTHOREY, P. A.;BLOCK, A. J.;RONFELD, R. A.;MCMASTER, P. D.;BYRNES, E. W+, J. MED. CHEM., 1981, 24, N 7, 798-806
  作者：TENTHOREY, P. A.、BLOCK, A. J.、RONFELD, R. A.、MCMASTER, P. D.、BYRNES, E. W+

  DOI：——

  日期：——
• US4558129A
  申请人：——

  公开号：US4558129A

  公开（公告）日：1985-12-10