(+)-1,2,3,6-tetrahydro-1-{N-[[4-(2-nitrophenyl)piperazin-1-yl]propyl]carboxamido}-4-methyl-6-(3,4-difluorophenyl)-2-oxopyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (+)-1,2,3,6-tetrahydro-1-{N-[[4-(2-nitrophenyl)piperazin-1-yl]propyl]carboxamido}-4-methyl-6-(3,4-difluorophenyl)-2-oxopyrimidine
• 英文别名: 4-(3,4-Difluoro-phenyl)-6-methyl-3-{3-[4-(2-nitro-phenyl)-piperazin-1-yl]-propylcarbamoyl}-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester；methyl 4-(3,4-difluorophenyl)-6-methyl-3-[3-[4-(2-nitrophenyl)piperazin-1-yl]propylcarbamoyl]-2-oxo-1,4-dihydropyrimidine-5-carboxylate
• 化学式: C₂₇H₃₀F₂N₆O₆
• 分子量: 572.569
• InChiKey: QORSFUXHRJFURF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  140
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  6-(3,4-difluorophenyl)-5-methoxycarbonyl-4-methyl-1-[(4-nitrophenyloxy)carbonyl]-2-oxo-1,2,3,6-tetrahydropyrimidine 在 碳酸氢钠 、 potassium iodide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 10.0h， 生成 (+)-1,2,3,6-tetrahydro-1-{N-[[4-(2-nitrophenyl)piperazin-1-yl]propyl]carboxamido}-4-methyl-6-(3,4-difluorophenyl)-2-oxopyrimidine
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Antagonists. 3. Approaches To Eliminate Opioid Agonist Metabolites by Using Substituted Phenylpiperazine Side Chains

  摘要：

  Dihydropyrimidinones, such as 1, represent a novel class of alpha(1a) adrenoceptor antagonists with potential for the treatment of benign prostatic hyperplasia (BPH) (see part 1 of this series). Analysis of the metabolites of 1 revealed that 4-methoxycarbonyl-4-phenylpiperidine is formed as the major metabolite and is an agonist at the mu-opioid receptor. To circumvent any potential liability resulting from the metabolite, we decided to identify alternate templates devoid of agonist activity at the mu-opioid receptor to replace the 4-methoxycarbonyl-4-phenylpiperidine moiety. The present study describes the synthesis and SAR of dihydropyrimidinones linked to substituted 4-phenylpiperazine containing side chains. Compound (+)-38 was identified as a lead compound with a binding and functional profile comparable to that of 1. The putative metabolite 2-carboxamidophenylpiperazine has negligible affinity for the mu-opioid receptor.

  DOI：

  10.1021/jm990202+