(2Z)-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylideneethanoic acid | 866761-70-8

• 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: (2Z)-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylideneethanoic acid
• 英文别名: R-125689；Acetic acid, 2-((4R)-1-((1R)-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4-mercapto-3-piperidinylidene)-, (2Z)-；(2Z)-2-[(4R)-1-[(1R)-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene]acetic acid
• CAS: 866761-70-8
• 化学式: C₁₈H₂₀FNO₃S
• 分子量: 349.426
• InChiKey: ZWUQVNSJSJHFPS-IKTMDDPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2Z)-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylideneethanoic acid 、 二甲基亚砜 在 乙二胺四乙酸 作用下， 以 aq. phosphate buffer 为溶剂， 生成 (2Z)-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylideneethanoic acid
  参考文献：
  名称：

  Hepatic Microsomal Thiol Methyltransferase Is Involved in Stereoselective Methylation of Pharmacologically Active Metabolite of Prasugrel

  摘要：

  RS和RR异构体。

  DOI：

  10.1124/dmd.114.057661

文献信息

• Hepatic Microsomal Thiol Methyltransferase Is Involved in Stereoselective Methylation of Pharmacologically Active Metabolite of Prasugrel
  作者：Miho Kazui、Katsunobu Hagihara、Takashi Izumi、Toshihiko Ikeda、Atsushi Kurihara

  DOI：10.1124/dmd.114.057661

  日期：2014.7

  Prasugrel, a thienopyridine antiplatelet drug, is converted in animals and humans to the pharmacologically active metabolite R-138727 [(2 Z )-1-[(1 RS )-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene}ethanoic acid], which has two chiral centers, occurring as a mixture of four isomers. The RS and RR isomers are more active than the SS and SR isomers (RS > RR > > SR = SS). The pharmacologically active metabolite is further metabolized to an S-methylated metabolite that is the major identified inactive metabolite in humans. In rat, dog, and human liver microsomes supplemented with S-adenosyl methione, the SS and SR isomers of the active metabolite were extensively S-methylated while the RS and RR isomers were not. Addition of 2,3-dichloromethyl benzylamine (50 µ M) completely inhibited the S-methylation reaction, indicating that the microsomal and cytosolic thiol methyltransferase but not the cytosolic thiopurine S-methyltransferase is involved in the methylation. The hepatic intrinsic clearance values for methylation of the RS, RR, SS, and SR isomers (ml/min/kg) were 0, 0, 40.4, and 37.6, respectively, in rat liver microsomes, 0, 0, 11.6, and 2.5, respectively, in dog liver microsomes, and 0, 0, 17.3, and 17.7, respectively, in human liver microsomes, indicating that the RS and RR isomers are not methylated in vitro and that the methylation of SS and SR isomers is high with rat > human > dog. This finding in vitro agreed well with the in vivo observation in rats and dogs, where the S-methylated SS and SR isomers were the major metabolites in the plasma whereas negligible amounts of S-methylated RS and RR isomers were detected after intravenous administration of the pharmacologically active metabolites.

  RS和RR异构体。