N,N-Diethyl-4-[(3-methoxy-phenyl)-(2,5,5-trimethyl-piperazin-1-yl)-methyl]-benzamide | 308109-97-9

• 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: N,N-Diethyl-4-[(3-methoxy-phenyl)-(2,5,5-trimethyl-piperazin-1-yl)-methyl]-benzamide
• 英文别名: N,N-diethyl-4-[(3-methoxyphenyl)-(2,5,5-trimethylpiperazin-1-yl)methyl]benzamide
• CAS: 308109-97-9
• 化学式: C₂₆H₃₇N₃O₂
• 分子量: 423.599
• InChiKey: HAILLLUQXQOSOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N,N-二乙基苯甲酰胺-4-羧醛 在 正丁基锂 、 氯化亚砜 、 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 50.5h， 生成 N,N-Diethyl-4-[(3-methoxy-phenyl)-(2,5,5-trimethyl-piperazin-1-yl)-methyl]-benzamide
  参考文献：
  名称：

  New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability

  摘要：

  Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl( 1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC50 = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)- methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, mu/delta = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.

  DOI：

  10.1021/jm000228x

文献信息

• Novel compounds with analgesic effect
  申请人：AstraZeneca Canada Inc.

  公开号：US20040138228A1

  公开（公告）日：2004-07-15

  Compounds of the formula (I) 1 as well as their pharmaceutically acceptable salts, and pharmaceutical compositions comprising the novel compounds. The novel compounds of the formula (I) are useful in the management of pain.

  式(I)的化合物及其药学上可接受的盐，以及包含这些新化合物的制药组合物。公式(I)的新化合物可用于疼痛管理。
• Novel diarylmethylpiperazine and diarylmethylphenyl compounds with analgesic effect
  申请人：AstraZeneca AB

  公开号：EP1408037A1

  公开（公告）日：2004-04-14

  Compounds of the formula (I) as well as their pharmaceutically acceptable salts, and pharmaceutical compositions comprising the novel compounds. The novel compounds of the formula (I) are useful in the management of pain.

  式 (I) 的化合物 及其药学上可接受的盐类，以及包含这些新型化合物的药物组合物。式（I）的新型化合物可用于治疗疼痛。
• NOVEL COMPOUNDS WITH ANALGESIC EFFECT
  申请人：Astra Pharma Inc.

  公开号：EP0915855A1

  公开（公告）日：1999-05-19
• US6130222A
  申请人：——

  公开号：US6130222A

  公开（公告）日：2000-10-10
• US6680321B1
  申请人：——

  公开号：US6680321B1

  公开（公告）日：2004-01-20