5,6-diphenyl-3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione | 1335107-07-7

• 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: 5,6-diphenyl-3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione
• 英文别名: 3-[2-[4-(2-Methoxyphenyl)piperazin-1-yl]ethyl]-5,6-diphenyl-1,7-dihydropyrrolo[2,3-d]pyrimidine-2,4-dione
• CAS: 1335107-07-7
• 化学式: C₃₁H₃₁N₅O₃
• 分子量: 521.619
• InChiKey: XUHINFLVZNNVDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-[[[(2-chloroethyl)amino]carbonyl]amino]-4,5-diphenyl-1H-pyrrole-3-carboxylic acid ethyl ester 在 碳酸氢钠 、 sodium iodide 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 22.0~120.0 ℃ 、1.03 MPa 条件下， 反应 24.25h， 生成 5,6-diphenyl-3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-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

文献信息

• Synthesis and molecular modeling of 1H-pyrrolopyrimidine-2,4-dione derivatives as ligands for the α1-adrenoceptors
  作者：Valeria Pittalà、Maria A. Siracusa、Maria N. Modica、Loredana Salerno、Alessandro Pedretti、Giulio Vistoli、Alfredo Cagnotto、Tiziana Mennini、Giuseppe Romeo

  DOI：10.1016/j.bmc.2011.06.043

  日期：2011.9

  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.