2-[N-[4-(1-tert-Butoxycarbonylpiperidin-4-yloxy)phenyl]-N-(4-methoxycarbonyl-benzoyl)aminomethyl]-1-(cyclohexylcarbamoylmethyl)-5-cyanobenzimidazole | 247133-80-8

• 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: 2-[N-[4-(1-tert-Butoxycarbonylpiperidin-4-yloxy)phenyl]-N-(4-methoxycarbonyl-benzoyl)aminomethyl]-1-(cyclohexylcarbamoylmethyl)-5-cyanobenzimidazole
• 英文别名: Tert-butyl 4-[4-[[5-cyano-1-[2-(cyclohexylamino)-2-oxoethyl]benzimidazol-2-yl]methyl-(4-methoxycarbonylbenzoyl)amino]phenoxy]piperidine-1-carboxylate
• CAS: 247133-80-8
• 化学式: C₄₂H₄₈N₆O₇
• 分子量: 748.879
• InChiKey: WTPHOSFVWBJDBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  55
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[N-[4-(1-tert-Butoxycarbonylpiperidin-4-yloxy)phenyl]-N-(4-methoxycarbonyl-benzoyl)aminomethyl]-1-(cyclohexylcarbamoylmethyl)-5-cyanobenzimidazole 在 吡啶 、 硫化氢 、 三乙胺 、 三氟乙酸 、 碘甲烷 作用下， 以 甲醇 、 氯仿 、 丙酮 为溶剂， 反应 16.08h， 生成 Methyl 4-[[5-carbamimidoyl-1-[2-(cyclohexylamino)-2-oxoethyl]benzimidazol-2-yl]methyl-(4-piperidin-4-yloxyphenyl)carbamoyl]benzoate
  参考文献：
  名称：

  Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data

  摘要：

  Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use in determining the role of Epi in the central nervous system. Here we demonstrate that a routinely used assay for screening PNMT inhibitors is not appropriate for those inhibitors having K-i values less than 1 muM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.009
• 作为产物：
  描述：

  4-(4-硝基苯氧基)四氢-1(2H)-吡啶羧酸叔丁酯 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 20.0~90.0 ℃ 、303.98 kPa 条件下， 反应 158.0h， 生成 2-[N-[4-(1-tert-Butoxycarbonylpiperidin-4-yloxy)phenyl]-N-(4-methoxycarbonyl-benzoyl)aminomethyl]-1-(cyclohexylcarbamoylmethyl)-5-cyanobenzimidazole
  参考文献：
  名称：

  Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data

  摘要：

  Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use in determining the role of Epi in the central nervous system. Here we demonstrate that a routinely used assay for screening PNMT inhibitors is not appropriate for those inhibitors having K-i values less than 1 muM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.009

文献信息

• Amidine compounds
  申请人：JAPAN TOBACCO INC.

  公开号：US20040006099A1

  公开（公告）日：2004-01-08

  A compound of the formula [I] 1 wherein R 1 , R 2 and R 3 are the same or different and each is hydrogen atom, hydroxy, lower alkyl or aryl, R is a group of the formula 2 wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the present invention, a salt thereof and a prodrug thereof are useful as factor Xa inhibitor and blood coagulation inhibitor, and are useful for the prophylaxis and/or treatment of diseases caused by blood coagulation or thrombus.

  化合物的式子为[I]1，其中R1、R2和R3相同或不同，且每个都是氢原子、羟基、低碳基或芳基，R是式子2的基团，其中每个符号如规范中定义的那样，其盐或前药。本发明的化合物、其盐和前药可用作因子Xa抑制剂和血液凝固抑制剂，并可用于预防和/或治疗由血液凝固或血栓引起的疾病。
• AMIDINE COMPOUNDS
  申请人：Japan Tobacco Inc.

  公开号：EP1070714A1

  公开（公告）日：2001-01-24

  Compounds represented by general formula [I] or salts thereof or prodrugs of the same [I] wherein R1, R2 end R3 are the same or different and each represents hydrogen, hydroxy, lower alkyl or aryl; and R represents formulas (a), (b) and (c) (wherein each symbol has the meaning as defined in the specification). These compounds, salts thereof or prodrugs of the same are useful as factor Xa inhibitors and anticoagulants and usable in preventing and/or treating diseases caused by blood coagulation or thrombi.

  通式[I]代表的化合物或其盐类或其原药[I]，其中R1、R2和R3是相同或不同的，各自代表氢、羟基、低级烷基或芳基；R代表式(a)、(b)和(c)（其中各符号具有说明书中定义的含义）。这些化合物、其盐类或其原药可作为 Xa 因子抑制剂和抗凝剂，用于预防和/或治疗由血液凝固或血栓引起的疾病。
• US6562828B1
  申请人：——

  公开号：US6562828B1

  公开（公告）日：2003-05-13
• Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data
  作者：Qian Wu、Kevin R Criscione、Gary L Grunewald、Michael J McLeish

  DOI：10.1016/j.bmcl.2004.06.009

  日期：2004.8

  Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use in determining the role of Epi in the central nervous system. Here we demonstrate that a routinely used assay for screening PNMT inhibitors is not appropriate for those inhibitors having K-i values less than 1 muM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported. (C) 2004 Elsevier Ltd. All rights reserved.