toluene-4-sulfonic acid 6-amino-2-(2-(tert-butoxycarbonylamino)-ethylsulfanyl)-pyrimidin-4-yl ester | 1178896-29-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: toluene-4-sulfonic acid 6-amino-2-(2-(tert-butoxycarbonylamino)-ethylsulfanyl)-pyrimidin-4-yl ester
• 英文别名: [6-Amino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylsulfanyl]pyrimidin-4-yl] 4-methylbenzenesulfonate
• CAS: 1178896-29-1
• 化学式: C₁₈H₂₄N₄O₅S₂
• 分子量: 440.544
• InChiKey: QIXVMDLZEXPAAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  toluene-4-sulfonic acid 6-amino-2-(2-(tert-butoxycarbonylamino)-ethylsulfanyl)-pyrimidin-4-yl ester 在 三氟乙酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 0.67h， 以87%的产率得到toluene-4-sulfonic acid 6-amino-2-(2-aminoethylsulfanyl)-pyrimidin-4-yl ester
  参考文献：
  名称：

  6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y12 receptors

  摘要：

  P2Y(12) plays an important role in platelet aggregation, which makes it an interesting target for antithrombotic agents. Compounds that antagonize P2Y(12) include the active metabolites of thienopyridines and molecules that are structurally related to ATP, which is an antagonist of P2Y(12). During the last few years, our group has been working on the development of P2Y(12) receptors antagonists that are based on an extremely simple chemical structure, the 6-amino-2-mercapto-3H-pyrimidin-4-one, variously substituted at the sulfur and oxygen functions. This nucleus represents the simplified combination of two known P2Y(12) antagonists: the active metabolite of the thienopyridines and ATP derivatives. The effects of the synthesized compounds were tested on ADP-induced human platelet aggregation, using light transmission aggregometry. None of the tested compounds induced platelet aggregation, while some of them, at concentration of 10 (4) M, partially inhibited platelet aggregation induced by ADP 10 (6) M. The most potent compound, 6b, antagonized the inhibitory effect of 2-methylthio-ADP on the forskolin-induced accumulation of cyclic-AMP in CHO FlpIN cells expressing recombinant human P2Y(12)-receptors. In addition, none of the tested compounds, including 6b, interfered with ligand binding to P1 receptors. Our results suggest that some of the synthesized compounds are specific antagonists of P2 receptors, and in particular of P2Y(12) and suggest that further development of this structurally new series of compounds as P2Y(12) receptors antagonists is recommended. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.061
• 作为产物：
  描述：

  [2-(4-amino-6-oxo-1,6-dihydro-pyrimidin-2-ylsulfanyl)-ethyl]-carbamic acid tert-butyl ester 、 对甲苯磺酰氯 在 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 以71%的产率得到toluene-4-sulfonic acid 6-amino-2-(2-(tert-butoxycarbonylamino)-ethylsulfanyl)-pyrimidin-4-yl ester
  参考文献：
  名称：

  6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y12 receptors

  摘要：

  P2Y(12) plays an important role in platelet aggregation, which makes it an interesting target for antithrombotic agents. Compounds that antagonize P2Y(12) include the active metabolites of thienopyridines and molecules that are structurally related to ATP, which is an antagonist of P2Y(12). During the last few years, our group has been working on the development of P2Y(12) receptors antagonists that are based on an extremely simple chemical structure, the 6-amino-2-mercapto-3H-pyrimidin-4-one, variously substituted at the sulfur and oxygen functions. This nucleus represents the simplified combination of two known P2Y(12) antagonists: the active metabolite of the thienopyridines and ATP derivatives. The effects of the synthesized compounds were tested on ADP-induced human platelet aggregation, using light transmission aggregometry. None of the tested compounds induced platelet aggregation, while some of them, at concentration of 10 (4) M, partially inhibited platelet aggregation induced by ADP 10 (6) M. The most potent compound, 6b, antagonized the inhibitory effect of 2-methylthio-ADP on the forskolin-induced accumulation of cyclic-AMP in CHO FlpIN cells expressing recombinant human P2Y(12)-receptors. In addition, none of the tested compounds, including 6b, interfered with ligand binding to P1 receptors. Our results suggest that some of the synthesized compounds are specific antagonists of P2 receptors, and in particular of P2Y(12) and suggest that further development of this structurally new series of compounds as P2Y(12) receptors antagonists is recommended. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.061

文献信息

• 6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y12 receptors
  作者：Pamela Crepaldi、Barbara Cacciari、Maria-Cruz Bonache、Giampiero Spalluto、Katia Varani、Pier Andrea Borea、Ivar von Kügelgen、Kristina Hoffmann、Mariateresa Pugliano、Cristina Razzari、Marco Cattaneo

  DOI：10.1016/j.bmc.2009.04.061

  日期：2009.7

  P2Y(12) plays an important role in platelet aggregation, which makes it an interesting target for antithrombotic agents. Compounds that antagonize P2Y(12) include the active metabolites of thienopyridines and molecules that are structurally related to ATP, which is an antagonist of P2Y(12). During the last few years, our group has been working on the development of P2Y(12) receptors antagonists that are based on an extremely simple chemical structure, the 6-amino-2-mercapto-3H-pyrimidin-4-one, variously substituted at the sulfur and oxygen functions. This nucleus represents the simplified combination of two known P2Y(12) antagonists: the active metabolite of the thienopyridines and ATP derivatives. The effects of the synthesized compounds were tested on ADP-induced human platelet aggregation, using light transmission aggregometry. None of the tested compounds induced platelet aggregation, while some of them, at concentration of 10 (4) M, partially inhibited platelet aggregation induced by ADP 10 (6) M. The most potent compound, 6b, antagonized the inhibitory effect of 2-methylthio-ADP on the forskolin-induced accumulation of cyclic-AMP in CHO FlpIN cells expressing recombinant human P2Y(12)-receptors. In addition, none of the tested compounds, including 6b, interfered with ligand binding to P1 receptors. Our results suggest that some of the synthesized compounds are specific antagonists of P2 receptors, and in particular of P2Y(12) and suggest that further development of this structurally new series of compounds as P2Y(12) receptors antagonists is recommended. (C) 2009 Elsevier Ltd. All rights reserved.