5-(cyanoethoxycarbonyl)-1-{N-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propyl]carboxamido}-4-methyl-6-(4-nitrophenyl)-2-oxo-1,2,3,6-tetrahydropyrimidine | 251930-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 5-(cyanoethoxycarbonyl)-1-{N-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propyl]carboxamido}-4-methyl-6-(4-nitrophenyl)-2-oxo-1,2,3,6-tetrahydropyrimidine
• 英文别名: 2-Cyanoethyl 3-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propylcarbamoyl]-6-methyl-4-(4-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate
• CAS: 251930-34-4
• 化学式: C₃₂H₃₆N₆O₈
• 分子量: 632.673
• InChiKey: NLKFCEZSKSXSBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  187
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-(cyanoethoxycarbonyl)-1-{N-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propyl]carboxamido}-4-methyl-6-(4-nitrophenyl)-2-oxo-1,2,3,6-tetrahydropyrimidine 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 以89%的产率得到3-[3-(4-Methoxycarbonyl-4-phenyl-piperidin-1-yl)-propylcarbamoyl]-6-methyl-4-(4-nitro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Antagonists. 1. Structure−Activity Relationship in Dihydropyrimidinones

  摘要：

  Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K-i = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K-b(DBP)/K-b(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

  DOI：

  10.1021/jm990200p
• 作为产物：
  描述：

  2-cyanoethyl 2-methoxy-6-methyl-4-(4-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate 在 盐酸 、 碳酸氢钠 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 5-(cyanoethoxycarbonyl)-1-{N-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propyl]carboxamido}-4-methyl-6-(4-nitrophenyl)-2-oxo-1,2,3,6-tetrahydropyrimidine
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Antagonists. 1. Structure−Activity Relationship in Dihydropyrimidinones

  摘要：

  Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K-i = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K-b(DBP)/K-b(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

  DOI：

  10.1021/jm990200p

文献信息

• Design and Synthesis of Novel α₁_a Adrenoceptor-Selective Antagonists. 1. Structure−Activity Relationship in Dihydropyrimidinones
  作者：Dhanapalan Nagarathnam、Shou Wu Miao、Bharat Lagu、George Chiu、James Fang、T. G. Murali Dhar、Jack Zhang、Sriram Tyagarajan、Mohammad R. Marzabadi、Fengqi Zhang、Wai C. Wong、Wanying Sun、Dake Tian、John M. Wetzel、Carlos Forray、Raymond S. L. Chang、Theodore P. Broten、Richard W. Ransom、Terry W. Schorn、Tsing B. Chen、Stacey O'Malley、Paul Kling、Kathryn Schneck、Robert Bendesky、Charles M. Harrell、Kamlesh P. Vyas、Charles Gluchowski

  DOI：10.1021/jm990200p

  日期：1999.11.1

  Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K-i = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K-b(DBP)/K-b(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.