1-[4-methyl-6-(isopropylamino)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide | 1439923-15-5

• 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-[4-methyl-6-(isopropylamino)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide
• 英文别名: 1-[4-methyl-6-(propan-2-ylamino)-1,3,5-triazin-2-yl]-N-[[2-(trifluoromethyl)phenyl]methyl]piperidine-4-carboxamide
• CAS: 1439923-15-5
• 化学式: C₂₁H₂₇F₃N₆O
• 分子量: 436.48
• InChiKey: JQHCYQUHJQOVNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(三氟甲基)苄胺 在 甲醇 、 4-二甲氨基吡啶 、 氨 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.25h， 生成 1-[4-methyl-6-(isopropylamino)-1,3,5-triazin-2-yl]-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

• 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.