5-chloropentano-2',6'-xylidide | 77470-78-1

• 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: 5-chloropentano-2',6'-xylidide
• 英文别名: 5-chloro-N-(2,6-dimethylphenyl)pentanamide
• CAS: 77470-78-1
• 化学式: C₁₃H₁₈ClNO
• 分子量: 239.745
• InChiKey: BVGJCVZEYUJCEU-UHFFFAOYSA-N

物化性质

• 熔点：
  86-86.5 °C
• 沸点：
  377.2±30.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-chloropentano-2',6'-xylidide 在 二乙胺盐酸盐 、 sodium cyanoborohydride 、 N,N'-二环己基碳二亚胺 、 sodium iodide 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 72.0h， 生成 5-(diethylamino)hexano-2',6'-xylidide
  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-氯代戊酰氯 、 2,6-二甲基苯胺 以 乙醚 为溶剂， 反应 1.0h， 以84%的产率得到5-chloropentano-2',6'-xylidide
  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

• 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：——
• Substituted aniline derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0198325B1

  公开（公告）日：1992-07-15
• US4696930A
  申请人：——

  公开号：US4696930A

  公开（公告）日：1987-09-29
• US4891429A
  申请人：——

  公开号：US4891429A

  公开（公告）日：1990-01-02
• New antiarrhythmic agents. 6. Quantitative structure-activity relationships of aminoxylidides
  作者：Paul A. Tenthorey、Alan J. Block、Robert A. Ronfeld、Paul D. McMaster、Eugene W. Byrnes

  DOI：10.1021/jm00139a007

  日期：1981.7

  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.