N,N-diethyl-4-[hydroxy(quinolin-4-yl)methyl]benzamide | 308110-37-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N,N-diethyl-4-[hydroxy(quinolin-4-yl)methyl]benzamide
• CAS: 308110-37-4
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: FSFLXTLZAXPJJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N,N-diethyl-4-[hydroxy(quinolin-4-yl)methyl]benzamide 在 氯化亚砜 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 13.0h， 生成 N,N-Diethyl-4-(piperazin-1-yl-quinolin-4-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
• 作为产物：
  描述：

  4-喹啉甲醛 、 N,N-二乙基-4-碘苯甲酰胺 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以51%的产率得到N,N-diethyl-4-[hydroxy(quinolin-4-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

• New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability
  作者：Niklas Plobeck、Daniel Delorme、Zhong-Yong Wei、Hua Yang、Fei Zhou、Peter Schwarz、Lars Gawell、Hélène Gagnon、Benjamin Pelcman、Ralf Schmidt、Shi Yi Yue、Christopher Walpole、William Brown、Edward Zhou、Maryse Labarre、Kemal Payza、Stephane St-Onge、Augustus Kamassah、Pierre-Emmanuel Morin、Denis Projean、Julie Ducharme、Edward Roberts

  DOI：10.1021/jm000228x

  日期：2000.10.1

  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.