N,N-diethyl-2-(4-(2-N-benzyloxycarbamyllethyl)phenoxy)acetamide | 245078-44-8

• 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-2-(4-(2-N-benzyloxycarbamyllethyl)phenoxy)acetamide
• 英文别名: benzyl N-[2-[4-[2-(diethylamino)-2-oxoethoxy]phenyl]ethyl]carbamate
• CAS: 245078-44-8
• 化学式: C₂₂H₂₈N₂O₄
• 分子量: 384.475
• InChiKey: NXYIZTMPJJJLAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-diethyl-2-(4-(2-N-benzyloxycarbamyllethyl)phenoxy)acetamide 在 palladium on activated charcoal dimethyl sulfide borane 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 14.5h， 生成 N-(2-(4-(2-diethylaminoethoxy)phenyl)ethyl)-4-chlorocinnamide hydrochloride
  参考文献：
  名称：

  Structure−Activity Relationship of N-(Phenylalkyl)cinnamides as Novel NR2B Subtype-Selective NMDA Receptor Antagonists

  摘要：

  A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC50 value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.

  DOI：

  10.1021/jm990199u
• 作为产物：
  描述：

  苄基N-[2-(4-羟基苯基)乙基]氨基甲酸酯 、 N,N-diethyl-2-iodoacetamide 在 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以92%的产率得到N,N-diethyl-2-(4-(2-N-benzyloxycarbamyllethyl)phenoxy)acetamide
  参考文献：
  名称：

  Structure−Activity Relationship of N-(Phenylalkyl)cinnamides as Novel NR2B Subtype-Selective NMDA Receptor Antagonists

  摘要：

  A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC50 value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.

  DOI：

  10.1021/jm990199u