2-(4-formyl-1H-1,2,3-triazol-1-yl)acetic acid | 1175146-73-2

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(4-formyl-1H-1,2,3-triazol-1-yl)acetic acid
• 英文别名: 2-(4-formyltriazol-1-yl)acetic acid
• CAS: 1175146-73-2
• 化学式: C₅H₅N₃O₃
• mdl: MFCD20660491
• 分子量: 155.113
• InChiKey: KSGBEEROVNQAAB-UHFFFAOYSA-N

物化性质

• 沸点：
  434.6±51.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  85.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-formyl-1H-1,2,3-triazol-1-yl)acetic acid 、 N-去异丙基普萘洛尔 在 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  GPCR 的片段进化：二级结合位点在优化中的作用

  摘要：

  我们开发了一种基于对接的片段进化方法，将正构片段扩展到不太保守的 GPCR 二级结合口袋。我们合成并测试了 112 个双位分子，评估了 13 000 次 β 1 - 和 β 2 -肾上腺素能受体的延伸。我们的结果证实了二级结合口袋对效力和选择性优化的积极贡献。

  DOI：

  10.1039/d1cc04636e
• 作为产物：
  描述：

  (4-Diethoxymethyl-[1,2,3]triazol-1-yl)-acetic acid 在 盐酸 、 水 作用下， 生成 2-(4-formyl-1H-1,2,3-triazol-1-yl)acetic acid
  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

• Fragment evolution for GPCRs: the role of secondary binding sites in optimization
  作者：Florent Chevillard、Ádám Kelemen、Jillian G. Baker、Vivien A. Aranyodi、Frank Balzer、Peter Kolb、György M. Keserű

  DOI：10.1039/d1cc04636e

  日期：——

  We developed a docking-based fragment evolution approach that extends orthosteric fragments towards a less conserved secondary binding pocket of GPCRs. Evaluating 13 000 extensions for the β1- and β2-adrenergic receptors we synthesized and tested 112 bitopic molecules. Our results confirmed the positive contribution of the secondary binding pocket to both potency and selectivity optimizations.

  我们开发了一种基于对接的片段进化方法，将正构片段扩展到不太保守的 GPCR 二级结合口袋。我们合成并测试了 112 个双位分子，评估了 13 000 次 β 1 - 和 β 2 -肾上腺素能受体的延伸。我们的结果证实了二级结合口袋对效力和选择性优化的积极贡献。
• 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.