4-[3-(6-Methylpyridin-3-yl)-1h-1,2,4-triazol-1-yl]aniline | 1129541-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-[3-(6-Methylpyridin-3-yl)-1h-1,2,4-triazol-1-yl]aniline
• 英文别名: 4-[3-(6-methylpyridin-3-yl)-1,2,4-triazol-1-yl]aniline
• CAS: 1129541-11-2
• 化学式: C₁₄H₁₃N₅
• 分子量: 251.291
• InChiKey: QLVYSVGBSCYXKJ-UHFFFAOYSA-N

物化性质

• 沸点：
  495.7±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-(6-Methylpyridin-3-yl)-1h-1,2,4-triazol-1-yl]aniline 、 在 palladium diacetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 5-fluoro-4-(1-methyl-1H-pyrazol-3-yl)-N-(4-(3-(6-methylpyridin-3-yl)-1H-1,2,4-triazol-1-yl)phenyl)pyridin-2-amine
  参考文献：
  名称：

  Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase inhibitors

  摘要：

  The design and synthesis of a novel series of c-jun N-terminal kinase (JNK) inhibitors is described. The development of the 4-(pyrazol-3-yl)-pyridine series was discovered from an earlier pyrimidine series of JNK inhibitors. Through the optimization of the scaffold 2, several potent compounds with good in vivo profiles were discovered. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.104

文献信息

• [EN] SUBSTITUTED PYRIMIDINYL-AMINES AS PROTEIN KINASE INHIBITORS<br/>[FR] PYRIMIDINYL-AMINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE LA PROTÉINE KINASE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2009032861A1

  公开（公告）日：2009-03-12

  The present invention provides novel substituted pyrimidinyl-amines that are useful as inhibitors of protein kinases, especially c-Jun N-terminal kinases (JNK) and pharmaceutical compositions thereof and methods of using the same for treating conditions responsive to the inhibition of the JNK pathway.

  本发明提供了一种新型的取代嘧啶基胺，可用作蛋白激酶抑制剂，特别是c-Jun N-末端激酶（JNK）的抑制剂，以及包含它们的药物组合物和使用相同的方法来治疗对JNK途径抑制敏感的疾病。
• SUBSTITUTED PYRIMIDINYL-AMINES AS PROTEIN KINASE INHIBITORS
  申请人：Kamenecka Theodore Mark

  公开号：US20130231336A1

  公开（公告）日：2013-09-05

  The present invention provides novel substituted pyrimidinyl-amines that are useful as inhibitors of protein kinases, especially c-Jun N-terminal kinases (JNK) and pharmaceutical compositions thereof and methods of using the same for treating conditions responsive to the inhibition of the JNK pathway.

  本发明提供了一种新型的取代嘧啶基胺，可用作蛋白激酶抑制剂，特别是c-Jun N末端激酶（JNK）的抑制剂，以及其药物组合物和使用同样治疗对JNK通路抑制有响应的疾病的方法。
• Lead Optimization toward Proof-of-Concept Tools for Huntington’s Disease within a 4-(1<i>H</i>-Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors
  作者：John Wityak、Kevin F. McGee、Michael P. Conlon、Ren Hua Song、Bryan C. Duffy、Brent Clayton、Michael Lynch、Gwen Wang、Emily Freeman、James Haber、Douglas B. Kitchen、David D. Manning、Jiffry Ismail、Yuri Khmelnitsky、Peter Michels、Jeff Webster、Macarena Irigoyen、Michele Luche、Monica Hultman、Mei Bai、IokTeng D. Kuok、Ryan Newell、Marieke Lamers、Philip Leonard、Dawn Yates、Kim Matthews、Lynette Ongeri、Steve Clifton、Tania Mead、Susan Deupree、Pat Wheelan、Kathy Lyons、Claire Wilson、Alex Kiselyov、Leticia Toledo-Sherman、Maria Beconi、Ignacio Muñoz-Sanjuan、Jonathan Bard、Celia Dominguez

  DOI：10.1021/jm5013598

  日期：2015.4.9

  Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.
• Synthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) Inhibitors
  作者：Yuanjun He、Theodore M. Kamenecka、Youseung Shin、Xinyi Song、Rong Jiang、Romain Noel、Derek Duckett、Weimin Chen、Yuan Yuan Ling、Michael D. Cameron、Li Lin、Susan Khan、Marcel Koenig、Philip V. LoGrasso

  DOI：10.1016/j.bmcl.2011.01.079

  日期：2011.3

  Quinazoline 3 was discovered as a novel c-jun N-terminal kinase (JNK) inhibitor with good brain penetration and pharmacokinetic (PK) properties. A number of analogs which were potent both in the biochemical and cellular assays were discovered. Quinazoline 13a was found to be a potent JNK3 inhibitor (IC50 = 40 nM), with > 500-fold selectivity over p38, and had good PK and brain penetration properties. With these properties, 13a is considered a potential candidate for in vivo evaluation. (C) 2011 Elsevier Ltd. All rights reserved.
• US8530480B2
  申请人：——

  公开号：US8530480B2

  公开（公告）日：2013-09-10