R-106583(普拉格雷代谢物) | 916599-27-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: R-106583(普拉格雷代谢物)
• 英文名称: R-106583
• 英文别名: (2Z)-{1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-(methylsulfanyl)piperidin-3-ylidene}ethanoic acid；R-106583 (Prasugrel Metabolite)；(2Z)-2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-methylsulfanylpiperidin-3-ylidene]acetic acid
• CAS: 916599-27-4
• 化学式: C₁₉H₂₂FNO₃S
• 分子量: 363.453
• InChiKey: UUMYYIQRSCXALD-RAXLEYEMSA-N

物化性质

• 沸点：
  525.1±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  二甲基亚砜 、 R-138727 在 乙二胺四乙酸 作用下， 以 aq. phosphate buffer 为溶剂， 生成 R-106583(普拉格雷代谢物)
  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

• Acid addition salts of hydropyridine derivatives
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20030134872A1

  公开（公告）日：2003-07-17

  Acid addition salts of 2-acetoxy-5-(&agr;-cyclopropyl-carbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine. The acid addition salts of tetrahydrothienopyridine derivatives of the present invention exhibit excellent oral absorption, metabolization into the active compound, and platelet aggregation-inhibiting effects, low toxicity, and excellent storage and handling stabilities, and are useful as medicaments, preferably preventive or therapeutic agents (particularly therapeutic agents) for diseases caused by a thrombus or an embolus, still more preferably preventive or therapeutic agents (particularly therapeutic agents) for thrombosis or embolism.

  2-乙酰氧基-5-(&agr;-环丙基羰基-2-氟苯甲基)-4,5,6,7-四氢噻吩[3,2-c]吡啶的酸盐。本发明的四氢噻吩吡啶衍生物的酸盐表现出优异的口服吸收性能，代谢为活性化合物，抑制血小板聚集作用，低毒性，优秀的储存和处理稳定性，并且可作为药物使用，最好是预防或治疗剂（特别是治疗剂），用于由血栓或栓塞引起的疾病，更好地是预防或治疗剂（特别是治疗剂）用于血栓形成或栓塞。
• HYDROPYRIDINE DERIVATIVE ACID ADDITION SALTS
  申请人：Sankyo Company, Limited

  公开号：EP1298132B1

  公开（公告）日：2006-11-22
• US6693115B2
  申请人：——

  公开号：US6693115B2

  公开（公告）日：2004-02-17
• 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。