1-[2-methyl-6-(methylamino)-4-pyrimidinyl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide | 1176761-04-8

• 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: 1-[2-methyl-6-(methylamino)-4-pyrimidinyl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide
• 英文别名: 1-[2-methyl-6-(methylamino)pyrimidin-4-yl]-N-[[2-(trifluoromethyl)phenyl]methyl]piperidine-4-carboxamide
• CAS: 1176761-04-8
• 化学式: C₂₀H₂₄F₃N₅O
• 分子量: 407.439
• InChiKey: RTBQCHQUSCVRES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl 4-((2-(trifluoromethyl)benzyl)carbamoyl)piperidine-1-carboxylate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 74.0h， 生成 1-[2-methyl-6-(methylamino)-4-pyrimidinyl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide
  参考文献：
  名称：

  Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase

  摘要：

  1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[[4-bromo-2-(trifluoromethoxy)]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.04.019

文献信息

• [EN] NOVEL sEH INHIBITORS AND THEIR USE<br/>[FR] NOUVEAUX INHIBITEURS DE sEH ET LEUR UTILISATION
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009097476A1

  公开（公告）日：2009-08-06

  The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme. Specifically, the invention is directed to compounds according to Formula (I) wherein R1, R2, R3, R5a, R6a, A, B, K, L, M, Y, Z, I, and m are defined herein, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are sEH inhibitors and can be used in the treatment of diseases mediated by the sEH enzyme, such as hypertension. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting sEH and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及新型sEH抑制剂及其在通过sEH酶介导的疾病治疗中的应用。具体而言，该发明涉及符合以下式（I）的化合物，其中R1、R2、R3、R5a、R6a、A、B、K、L、M、Y、Z、I和m在此处定义，并其药用盐。该发明的化合物是sEH抑制剂，可用于治疗通过sEH酶介导的疾病，如高血压。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制sEH和治疗相关症状的方法。
• Novel sEH Inhibitors and their Use
  申请人：Marino, JR. Joseph Paul

  公开号：US20100311776A1

  公开（公告）日：2010-12-09

  The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme. Specifically, the invention is directed to compounds according to Formula I: wherein R1, R2, R3, R5a, R6a, A, B, K, L, M, Y, Z, l, and m are defined herein, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are sEH inhibitors and can be used in the treatment of diseases mediated by the sEH enzyme, such as hypertension. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting sEH and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及新型sEH抑制剂及其在治疗由sEH酶介导的疾病中的应用。具体而言，本发明涉及按式I所示的化合物：其中R1、R2、R3、R5a、R6a、A、B、K、L、M、Y、Z、l和m在此被定义，并且其药学上可接受的盐。本发明的化合物是sEH抑制剂，可用于治疗由sEH酶介导的疾病，如高血压。因此，本发明还涉及包括本发明化合物的制药组合物。本发明还进一步涉及使用本发明化合物或包括本发明化合物的制药组合物来抑制sEH和治疗与此相关的疾病的方法。
• Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase
  作者：Reema K. Thalji、Jeff J. McAtee、Svetlana Belyanskaya、Martin Brandt、Gregory D. Brown、Melissa H. Costell、Yun Ding、Jason W. Dodson、Steve H. Eisennagel、Rusty E. Fries、Jeffrey W. Gross、Mark R. Harpel、Dennis A. Holt、David I. Israel、Larry J. Jolivette、Daniel Krosky、Hu Li、Quinn Lu、Tracy Mandichak、Theresa Roethke、Christine G. Schnackenberg、Benjamin Schwartz、Lisa M. Shewchuk、Wensheng Xie、David J. Behm、Stephen A. Douglas、Ami L. Shaw、Joseph P. Marino

  DOI：10.1016/j.bmcl.2013.04.019

  日期：2013.6

  1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[[4-bromo-2-(trifluoromethoxy)]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models. Published by Elsevier Ltd.