1-(Pyridin-4-ylmethyl)triazole-4-carbaldehyde | 1175146-75-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(Pyridin-4-ylmethyl)triazole-4-carbaldehyde
• CAS: 1175146-75-4
• 化学式: C₉H₈N₄O
• 分子量: 188.189
• InChiKey: NULZBFBAZUYQMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  60.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-氨基-8-氯-4-[(3-氯-4-氟苯基)氨基]-3-喹啉甲腈 、 1-(Pyridin-4-ylmethyl)triazole-4-carbaldehyde 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 8-chloro-4-[(3-chloro-4-fluorophenyl)amino]-6-({[1-(pyridin-4-ylmethyl)-1H-1,2,3-triazol-4-yl]methyl}amino)quinoline-3-carbonitrile
  参考文献：
  名称：

  Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-α production in human whole blood

  摘要：

  Tpl2 (cot/MAP3K8) is an upstream kinase of MEK in the ERK pathway. It plays an important role in Tumor Necrosis Factor-alpha (TNF-alpha) production and signaling. We have discovered that 8-halo-4-(3-chloro-4-fluorophenylamino)-6-[(1H-[ 1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles (4) are potent inhibitors of this enzyme. In order to improve the inhibition of TNF-alpha production in LPS-stimulated human blood, a series of analogs with a variety of substitutions around the triazole moiety were studied. We found that a cyclic amine group appended to the triazole ring could considerably enhance potency, aqueous solubility, and cell membrane permeability. Optimization of these cyclic amine groups led to the identification of 8-chloro-4-(3-chloro-4-fluorophenylamino)-6-((1-(1-ethylpiperidin-4-yl)-1H-1,2,3-triazol- 4-yl) methylamino)quinoline-3-carbonitrile (34). In a LPS-stimulated rat inflammation model, compound 34 showed good efficacy in inhibiting TNF-alpha production. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.009
• 作为产物：
  描述：

  4-[[4-(Diethoxymethyl)triazol-1-yl]methyl]pyridine 在 盐酸 、 水 作用下， 生成 1-(Pyridin-4-ylmethyl)triazole-4-carbaldehyde
  参考文献：
  名称：

  Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-α production in human whole blood

  摘要：

  Tpl2 (cot/MAP3K8) is an upstream kinase of MEK in the ERK pathway. It plays an important role in Tumor Necrosis Factor-alpha (TNF-alpha) production and signaling. We have discovered that 8-halo-4-(3-chloro-4-fluorophenylamino)-6-[(1H-[ 1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles (4) are potent inhibitors of this enzyme. In order to improve the inhibition of TNF-alpha production in LPS-stimulated human blood, a series of analogs with a variety of substitutions around the triazole moiety were studied. We found that a cyclic amine group appended to the triazole ring could considerably enhance potency, aqueous solubility, and cell membrane permeability. Optimization of these cyclic amine groups led to the identification of 8-chloro-4-(3-chloro-4-fluorophenylamino)-6-((1-(1-ethylpiperidin-4-yl)-1H-1,2,3-triazol- 4-yl) methylamino)quinoline-3-carbonitrile (34). In a LPS-stimulated rat inflammation model, compound 34 showed good efficacy in inhibiting TNF-alpha production. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.009

文献信息

• Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-α production in human whole blood
  作者：Junjun Wu、Neal Green、Rajeev Hotchandani、Yonghan Hu、Jeffrey Condon、Adrian Huang、Neelu Kaila、Huan-Qiu Li、Satenig Guler、Wei Li、Steve Y. Tam、Qin Wang、Jeffrey Pelker、Suzana Marusic、Sang Hsu、J. Perry Hall、Jean-Baptiste Telliez、Junqing Cui、Lih-Ling Lin

  DOI：10.1016/j.bmcl.2009.05.009

  日期：2009.7

  Tpl2 (cot/MAP3K8) is an upstream kinase of MEK in the ERK pathway. It plays an important role in Tumor Necrosis Factor-alpha (TNF-alpha) production and signaling. We have discovered that 8-halo-4-(3-chloro-4-fluorophenylamino)-6-[(1H-[ 1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles (4) are potent inhibitors of this enzyme. In order to improve the inhibition of TNF-alpha production in LPS-stimulated human blood, a series of analogs with a variety of substitutions around the triazole moiety were studied. We found that a cyclic amine group appended to the triazole ring could considerably enhance potency, aqueous solubility, and cell membrane permeability. Optimization of these cyclic amine groups led to the identification of 8-chloro-4-(3-chloro-4-fluorophenylamino)-6-((1-(1-ethylpiperidin-4-yl)-1H-1,2,3-triazol- 4-yl) methylamino)quinoline-3-carbonitrile (34). In a LPS-stimulated rat inflammation model, compound 34 showed good efficacy in inhibiting TNF-alpha production. (C) 2009 Elsevier Ltd. All rights reserved.