4-{3-[8-(5,6-dimethoxy-pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-benzoylamino}-benzoic acid | 1415314-02-1

• 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: 4-{3-[8-(5,6-dimethoxy-pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-benzoylamino}-benzoic acid
• 英文别名: 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)-[1,2,4]-triazolo[1,5-a]pyridin-6-yl)benzamido)benzoic acid；4-[[3-[8-[(5,6-Dimethoxypyridin-2-yl)amino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzoyl]amino]benzoic acid；4-[[3-[8-[(5,6-dimethoxypyridin-2-yl)amino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzoyl]amino]benzoic acid
• CAS: 1415314-02-1
• 化学式: C₂₇H₂₂N₆O₅
• 分子量: 510.509
• InChiKey: NOZNKSUEYWOQKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-氨基苯甲酸叔丁酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 sodium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 4-{3-[8-(5,6-dimethoxy-pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-benzoylamino}-benzoic acid
  参考文献：
  名称：

  Rational Design of Highly Selective Spleen Tyrosine Kinase Inhibitors

  摘要：

  A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is described. Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis, and SLE. Fostamatinib, a Syk inhibitor that successfully completed phase II clinical trials, also exhibits some undesirable side effects. More selective Syk inhibitors could offer safer, alternative treatments. Through a systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk ATP binding site as a rare combination among sequence aligned kinases and hypothesized that optimizing the interaction between them and a Syk inhibitor molecule would impart high selectivity for Syk over other kinases. We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our hypothesis and offer useful guidance to other researchers in the field.

  DOI：

  10.1021/jm301367c

文献信息

• TRIAZOLOPYRIDINE COMPOUNDS
  申请人：Hermann Johannes Cornelius

  公开号：US20120309746A1

  公开（公告）日：2012-12-06

  The present invention relates to the use of novel triazolopyridine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用以下式I的新型三唑吡啶衍生物： 其中所有变量取代基的定义如本文所述，这些化合物是SYK抑制剂，可用于治疗自身免疫和炎症性疾病。
• [EN] TRIAZOLOPYRIDINE COMPOUNDS<br/>[FR] COMPOSÉS DE TRIAZOLOPYRIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012163724A1

  公开（公告）日：2012-12-06

  The present invention relates to the use of novel triazolopyridine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用以下式I的新型三唑吡啶衍生物：其中所有变量取代基的定义如本文所述，这些衍生物是SYK抑制剂，可用于治疗自身免疫和炎症性疾病。
• Rational Design of Highly Selective Spleen Tyrosine Kinase Inhibitors
  作者：Matthew C. Lucas、David M. Goldstein、Johannes C. Hermann、Andreas Kuglstatter、Wenjian Liu、Kin Chun Luk、Fernando Padilla、Michelle Slade、Armando G. Villaseñor、Jutta Wanner、Wenwei Xie、Xiaohu Zhang、Cheng Liao

  DOI：10.1021/jm301367c

  日期：2012.12.13

  A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is described. Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis, and SLE. Fostamatinib, a Syk inhibitor that successfully completed phase II clinical trials, also exhibits some undesirable side effects. More selective Syk inhibitors could offer safer, alternative treatments. Through a systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk ATP binding site as a rare combination among sequence aligned kinases and hypothesized that optimizing the interaction between them and a Syk inhibitor molecule would impart high selectivity for Syk over other kinases. We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our hypothesis and offer useful guidance to other researchers in the field.