2-[[[[2-[4-(2-chlorophenyl)-1-piperazinyl]ethyl]amino]carbonyl]amino]-5-[4-(phenylmethoxy)phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester | 1335107-18-0

• 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: 2-[[[[2-[4-(2-chlorophenyl)-1-piperazinyl]ethyl]amino]carbonyl]amino]-5-[4-(phenylmethoxy)phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester
• CAS: 1335107-18-0
• 化学式: C₃₃H₃₆ClN₅O₄
• 分子量: 602.133
• InChiKey: PEBNNFRXTZMNPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.03
• 重原子数：
  43.0
• 可旋转键数：
  11.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  98.93
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-[[[[2-[4-(2-chlorophenyl)-1-piperazinyl]ethyl]amino]carbonyl]amino]-5-[4-(phenylmethoxy)phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester 在 potassium hydroxide 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 22.0~120.0 ℃ 、1.03 MPa 条件下， 反应 0.25h， 以63%的产率得到3-[2-[4-(2-chlorophenyl)-1-piperazinyl]ethyl]-6-[4-(phenylmethoxy)phenyl]-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione
  参考文献：
  名称：

  Synthesis and molecular modeling of 1H-pyrrolopyrimidine-2,4-dione derivatives as ligands for the α1-adrenoceptors

  摘要：

  Three different series of 1H-pyrrolopyrimidine-2,4-dione derivatives were designed and synthesized as ligands for the alpha(1)-adrenergic receptors (alpha(1)-ARs). A microwave-assisted protocol was developed in order to improve purity and yields of some final products. The majority of the synthesized compounds, tested in binding assays, displayed alpha(1)-AR affinities in the nanomolar range. Highest affinity values were found in derivatives 10b and 10c (K-i = 1.4 nM for both) whereas compound 10e was endowed with the best profile in term of alpha(1)-AR affinity (K-i = 2.71 nM) coupled with high selectivity towards 5-HT1A receptors (K-i > 10,000). Molecular docking studies were performed on human alpha(1)-ARs and human 5-HT1A receptors in order to rationalize the observed experimental affinity and selectivity; these computational studies helped to clarify molecular requirements for the design of high-selective alpha(1)-adrenergic ligands. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.043
• 作为产物：
  描述：

  3-氨基-3-亚氨基丙酸乙酯 在 碳酸氢钠 、 potassium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 32.0h， 生成 2-[[[[2-[4-(2-chlorophenyl)-1-piperazinyl]ethyl]amino]carbonyl]amino]-5-[4-(phenylmethoxy)phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and molecular modeling of 1H-pyrrolopyrimidine-2,4-dione derivatives as ligands for the α1-adrenoceptors

  摘要：

  Three different series of 1H-pyrrolopyrimidine-2,4-dione derivatives were designed and synthesized as ligands for the alpha(1)-adrenergic receptors (alpha(1)-ARs). A microwave-assisted protocol was developed in order to improve purity and yields of some final products. The majority of the synthesized compounds, tested in binding assays, displayed alpha(1)-AR affinities in the nanomolar range. Highest affinity values were found in derivatives 10b and 10c (K-i = 1.4 nM for both) whereas compound 10e was endowed with the best profile in term of alpha(1)-AR affinity (K-i = 2.71 nM) coupled with high selectivity towards 5-HT1A receptors (K-i > 10,000). Molecular docking studies were performed on human alpha(1)-ARs and human 5-HT1A receptors in order to rationalize the observed experimental affinity and selectivity; these computational studies helped to clarify molecular requirements for the design of high-selective alpha(1)-adrenergic ligands. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.043