1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[(4-bromo-2-trifluoromethoxy-phenyl)methyl]-4-piperidinecarboxamide | 1141896-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[(4-bromo-2-trifluoromethoxy-phenyl)methyl]-4-piperidinecarboxamide
• 英文别名: N-(4-bromo-2-(trifluoromethoxy)benzyl)-1-(4-methyl-6-(methylamino)-1,3,5-triazin-2-yl)piperidine-4-carboxamide；CB209579-078A3；GSK2188931A；N-({4-bromo-2-[(trifluoromethyl)oxy]phenyl}methyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxamide；N-(2-(Trifluoromethoxy)-4-bromobenzyl)-1-(4-(methylamino)-6-methyl-1,3,5-triazine-2-yl)piperidine-4-carboxamide；N-[[4-bromo-2-(trifluoromethoxy)phenyl]methyl]-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
• CAS: 1141896-04-9
• 化学式: C₁₉H₂₂BrF₃N₆O₂
• 分子量: 503.322
• InChiKey: PVTFEAGMCGMRRS-UHFFFAOYSA-N

物化性质

• 密度：
  1.504±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-溴-2-(三氟甲氧基)苯甲醛 在 氨 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 192.0h， 生成 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[(4-bromo-2-trifluoromethoxy-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] INHIBITEURS INÉDITS DE LA SEH ET LEUR UTILISATION
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009049165A1

  公开（公告）日：2009-04-16

  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: (I) wherein R1, R2, R3, R5a, R6a A, B, Y, x, and m are defined below, 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.

  该发明涉及新颖的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：(I) 其中R1、R2、R3、R5a、R6a、A、B、Y、x和m的定义如下，并且其药用盐。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和治疗与之相关的疾病的方法。
• NOVEL sEH INHIBITORS AND THEIR USE
  申请人：Ding Yun

  公开号：US20100210628A1

  公开（公告）日：2010-08-19

  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, Y, x, and m are defined below, 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定义的化合物，其中R1、R2、R3、R5a、R6a、A、B、Y、x和m如下所定义，以及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，本发明还涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物抑制sEH和治疗与其相关的疾病的方法。
• Diabetes and metabolic syndrome treatment with a novel dual modulator of soluble epoxide hydrolase and peroxisome proliferator-activated receptors
  申请人：The Medical College of Wisconsin, Inc.

  公开号：US10927069B2

  公开（公告）日：2021-02-23

  N-benzylbenzamides that act as dual soluble soluble epoxide hydrolase (sEH)/peroxisome proliferator-activated receptor γ (PPARγ) modulators and are useful as medications in the treatment of Metabolic Syndrome (MetS) cluster diseases, including diabetes. Methods of making and using the same are further provided.

  N-苄基苯甲酰胺作为双重可溶性环氧化物水解酶（sEH）/过氧化物酶体增殖激活受体γ（PPARγ）调节剂，可作为治疗代谢综合征（MetS）类疾病（包括糖尿病）的药物。此外，还提供了制造和使用这些药物的方法。
• Lanthanum(III) Triflate Catalyzed Direct Amidation of Esters
  作者：Hiroyuki Morimoto、Risa Fujiwara、Yuhei Shimizu、Kazuhiro Morisaki、Takashi Ohshima

  DOI：10.1021/ol500593v

  日期：2014.4.4

  Lanthanum trifluoromethanesulfonate is an effective single-component catalyst for synthesizing a variety of amides directly from esters and amines under mild conditions. Highly selective amidation of esters and amines, as well as catalyst-controlled amidation of esters, demonstrated the effectiveness of the catalyst system.
• NOVEL SEH INHIBITORS AND THEIR USE
  申请人：GlaxoSmithKline LLC

  公开号：EP2209376A1

  公开（公告）日：2010-07-28