1,1,2,2-tetradeutero-2-(thiophen-2-yl)ethanol | 1204688-12-9

• 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: 1,1,2,2-tetradeutero-2-(thiophen-2-yl)ethanol
• 英文别名: 1,1,2,2-d4-2-(thiophen-2-yl)ethanol；1,1,2,2-Tetradeuterio-2-thiophen-2-ylethanol
• CAS: 1204688-12-9
• 化学式: C₆H₈OS
• 分子量: 132.163
• InChiKey: VMJOFTHFJMLIKL-KHORGVISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,1,2,2-tetradeutero-2-(thiophen-2-yl)ethanol 在 盐酸 、 potassium hydrogencarbonate 、 三乙胺 作用下， 以 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 36.0h， 生成 (S)-methyl 2-(2-chlorophenyl)-2-(1,1,2,2-tetradeutero-2-(thiophen-2-yl)ethylamino)acetate hydrochloride
  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：

  噻吩-2-乙酸甲酯 在 硼氘化钠 、 sodium methylate 作用下， 以 四氢呋喃 、 氘代甲醇-d 为溶剂， 反应 2.58h， 生成 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

文献信息

• SUBSTITUTED 4-AMINO-PIPERIDINES
  申请人：Gant Thomas G.

  公开号：US20100016365A1

  公开（公告）日：2010-01-21

  The present invention relates to new substituted 4-amino-piperidine opioid receptor modulators, pharmaceutical compositions thereof, and methods of use thereof.

  本发明涉及新的取代4-氨基哌啶类阿片受体调节剂，其药物组成物以及使用方法。
• Deuterated Clopidogrel Analogues as a New Generation of Antiplatelet Agents
  作者：Yaoqiu Zhu、Jiang Zhou、Bo Jiao

  DOI：10.1021/ml300460t

  日期：2013.3.14

  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.