methyl 2,2-dideutero-2-(thiophen-2-yl)acetate | 112251-81-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: methyl 2,2-dideutero-2-(thiophen-2-yl)acetate
• 英文别名: methyl 2,2-dideuterio-2-thiophen-2-ylacetate
• CAS: 112251-81-7
• 化学式: C₇H₈O₂S
• 分子量: 158.189
• InChiKey: KNKIXYMOHMYZJR-BFWBPSQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.46
• 重原子数：
  10.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl 2,2-dideutero-2-(thiophen-2-yl)acetate 在 硼氘化钠 、 氘代甲醇-d 、 氯化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.58h， 以95%的产率得到1,1,2,2-tetradeutero-2-(thiophen-2-yl)ethanol
  参考文献：
  名称：

  Deuterated Clopidogrel Analogues as a New Generation of Antiplatelet Agents

  摘要：

  Clopidogrel (CPG) is an antithrombotic prodrug that needs hepatic cytochrome P450 (CYP) enzymes for its bioactivation. The clinical effects of CPG have been associated with high intersubject variability and a certain level of resistance. Recently, comprehensive biotransformation studies of CPG support that the observed clinical uncertainty stems from the low bioactivation efficiency, which is attributed to extensive attritional metabolism (e.g., hydrolysis of the methyl ester functionality and oxidation of the piperidine moiety). With the goal of potentiating the desired thiophene 2-oxidation through minimal structural modification, we have adopted the strategy of targeted metabolism shift and have designed and synthesized deuterated piperidine analogues of CPG. In vitro studies showed that the prodrug activation percentages have been significantly increased for the deuterated analogues as a result of stability enhancement of the piperidine moiety. In a pharmacological study with a rat model, oral administration of the deuterated analogues also demonstrated higher inhibitory activity than that of CPG against adenosine diphosphate (ADP) induced platelet aggregation. These deuterated analogues represent a new generation of antiplatelet agents with the potential to overcome the major clinical drawbacks of CPG.

  DOI：

  10.1021/ml300460t
• 作为产物：
  描述：

  2-噻吩乙酰氯 在 氘代甲醇-d 、 sodium methylate 作用下， 反应 2.5h， 生成 methyl 2,2-dideutero-2-(thiophen-2-yl)acetate
  参考文献：
  名称：

  Lee-Ruff, E.; Ablenas, Fred J., Canadian Journal of Chemistry, 1987, vol. 65, p. 1663 - 1667

  摘要：

  DOI：

文献信息

• LEE-RUFF, E.;ABLENAS, FRED J., CAN. J. CHEM., 65,(1987) N 7, 1663-1667
  作者：LEE-RUFF, E.、ABLENAS, FRED J.

  DOI：——

  日期：——