4-amino-6-(benzo[d][1,3]dioxol-5-yl)-2-((2-(4-nitrophenyl)-thiazol-4-yl)methylthio)pyrimidine-5-carbonitrile | 1589081-27-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 4-amino-6-(benzo[d][1,3]dioxol-5-yl)-2-((2-(4-nitrophenyl)-thiazol-4-yl)methylthio)pyrimidine-5-carbonitrile
• 英文别名: 4-Amino-6-(1,3-benzodioxol-5-yl)-2-[[2-(4-nitrophenyl)-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-5-carbonitrile；4-amino-6-(1,3-benzodioxol-5-yl)-2-[[2-(4-nitrophenyl)-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-5-carbonitrile
• CAS: 1589081-27-5
• 化学式: C₂₂H₁₄N₆O₄S₂
• 分子量: 490.523
• InChiKey: QPOVLBGWODYSTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  206
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  间氟苯甲酰胺 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 4-amino-6-(benzo[d][1,3]dioxol-5-yl)-2-((2-(4-nitrophenyl)-thiazol-4-yl)methylthio)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Agonists for the Adenosine A₁ Receptor with Tunable Residence Time. A Case for Nonribose 4-Amino-6-aryl-5-cyano-2-thiopyrimidines

  摘要：

  We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A(1) receptor (hA(1)AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.

  DOI：

  10.1021/jm401643m

文献信息

• Agonists for the Adenosine A₁ Receptor with Tunable Residence Time. A Case for Nonribose 4-Amino-6-aryl-5-cyano-2-thiopyrimidines
  作者：Julien Louvel、Dong Guo、Marta Agliardi、Tamara A. M. Mocking、Roland Kars、Tan Phát Pham、Lizi Xia、Henk de Vries、Johannes Brussee、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1021/jm401643m

  日期：2014.4.24

  We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A(1) receptor (hA(1)AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.