1-{3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl}-2-methoxy-5-methoxycarbonyl-4-methoxymethyl-6-(2,4,5-trifluorophenyl)-1,6-dihydropyrimidine | 253799-75-6

• 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-{3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl}-2-methoxy-5-methoxycarbonyl-4-methoxymethyl-6-(2,4,5-trifluorophenyl)-1,6-dihydropyrimidine
• CAS: 253799-75-6
• 化学式: C₃₀H₃₅F₃N₆O₆
• 分子量: 632.64
• InChiKey: OGZFJYLXMPAANL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  45.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  139.03
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  1-{3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl}-2-methoxy-5-methoxycarbonyl-4-methoxymethyl-6-(2,4,5-trifluorophenyl)-1,6-dihydropyrimidine 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以92%的产率得到3-{3-[4-(2-Carbamoyl-phenyl)-piperazin-1-yl]-propylcarbamoyl}-6-methoxymethyl-2-oxo-4-(2,4,5-trifluoro-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester
  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+
• 作为产物：
  描述：

  tert-butyl N-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propyl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 49.0h， 生成 1-{3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl}-2-methoxy-5-methoxycarbonyl-4-methoxymethyl-6-(2,4,5-trifluorophenyl)-1,6-dihydropyrimidine
  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+