2-(3,3,3-trifluoropropylthio)-5'-adenylic acid monoanhydride with dichloromethylenebis(phosphonic acid)

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 2-(3,3,3-trifluoropropylthio)-5'-adenylic acid monoanhydride with dichloromethylenebis(phosphonic acid)
• 英文别名: [[[[(2R,3S,4R,5R)-5-[6-amino-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-dichloromethyl]phosphonic acid
• 化学式: C₁₄H₁₉Cl₂F₃N₅O₁₂P₃S
• 分子量: 702.22
• InChiKey: ICLQQOJQUFCPOS-IOSLPCCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  295
• 氢给体数：
  7
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  坎格雷洛杂质 在 吡啶 、 甲醇 、 三正丁胺 、 磷酸三乙酯 、 碳酸氢钠 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 反应 5.75h， 生成 2-(3,3,3-trifluoropropylthio)-5'-adenylic acid monoanhydride with dichloromethylenebis(phosphonic acid)
  参考文献：
  名称：

  Antagonists of the Platelet P_2T Receptor:  A Novel Approach to Antithrombotic Therapy

  摘要：

  The platelet P(2T) receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P(2T) receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P(2T) receptor led to the identification of 10e (AR-C67085MX), having an IC(50) Of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P(2T) receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 101 (AR-C69931MX) having an IC(50) of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/lIIa antagonists.

  DOI：

  10.1021/jm981072s