tert-butyl N-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propyl]carbamate | 186347-45-5

• 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: tert-butyl N-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propyl]carbamate
• CAS: 186347-45-5
• 化学式: C₁₉H₃₀N₄O₃
• 分子量: 362.472
• InChiKey: JBBSWMFHBGPWKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  87.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  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 1.0h， 生成 1-(3-aminopropyl)-4-(2-carboxamidophenyl)piperazine
  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：

  1-(2-苯甲腈)哌嗪 在 硫酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 60.0h， 生成 tert-butyl N-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propyl]carbamate
  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+

文献信息

• Design and Synthesis of Novel α₁_a Adrenoceptor-Selective Antagonists. 3. Approaches To Eliminate Opioid Agonist Metabolites by Using Substituted Phenylpiperazine Side Chains
  作者：Bharat Lagu、Dake Tian、Dhanapalan Nagarathnam、Mohammad R. Marzabadi、Wai C. Wong、Shou W. Miao、Fengqi Zhang、Wanying Sun、George Chiu、James Fang、Carlos Forray、Raymond S. L. Chang、Richard W. Ransom、Tsing B. Chen、Stacey O'Malley、Kanyin Zhang、Kamlesh P. Vyas、Charles Gluchowski

  DOI：10.1021/jm990202+

  日期：1999.11.1

  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.