2-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid | 959585-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid
• 英文别名: 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid
• CAS: 959585-36-5
• 化学式: C₁₀H₁₀N₂O₂
• 分子量: 190.202
• InChiKey: DJTFJNNEGMZLLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid 在 氯化亚砜 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 2.5h， 生成 (S)-3-(1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazine
  参考文献：
  名称：

  Lessons from (S)-6-(1-(6-(1-Methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an Inhibitor of Receptor Tyrosine Kinase c-Met with High Protein Kinase Selectivity but Broad Phosphodiesterase Family Inhibition Leading to Myocardial Degeneration in Rats

  摘要：

  The hepatocyte growth factor (HGF)/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. An exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol -4-yl) - [1,2,4] triazolo [4,3-b pyridazin- 3-yl) ethyl) quinoline (8) was discovered from a highly selective high-throughput screening hit. via structure-based drug design and medicinal chemistry lead optimization. Compound 8 had many attractive properties meriting preclinical evaluation. Broad off-target screens identified 8 as a pan-phosphodiesterase (PDE) family inhibitor, which was implicated in a sustained increase in heart rate, increased cardiac output, and decreased contractility indices, as well as myocardial degeneration in in vivo safety evaluations in rats. Compound 8 was terminated as a preclinical candidate because of a narrow therapeutic window in cardio-related safety. The learning from multiparameter lead optimization and strategies to avoid the toxicity attrition at the late stage of drug discovery are discussed.

  DOI：

  10.1021/jm400926x
• 作为产物：
  描述：

  methyl 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)propionate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 生成 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid
  参考文献：
  名称：

  WO2007/138472

  摘要：

  公开号：

文献信息

• Compounds Useful as Immunomodulators
  申请人：Bristol-Myers Squibb Company

  公开号：US20150291549A1

  公开（公告）日：2015-10-15

  The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

  本公开涉及一般用作免疫调节剂的化合物。提供的是包含这些化合物的化合物、组合物以及它们的使用方法。本公开还涉及包含至少一种根据本公开的化合物的药物组合物，用于治疗各种疾病，包括癌症和传染病。
• TRIAZOLOPYRIDAZINE DERIVATIVES
  申请人：Pfizer Products Incorporated

  公开号：EP2032578A2

  公开（公告）日：2009-03-11
• US9850225B2
  申请人：——

  公开号：US9850225B2

  公开（公告）日：2017-12-26
• [EN] TRIAZOLOPYRIDAZINE DERIVATIVES<br/>[FR] DÉRIVÉS DE LA TRIAZOLOPYRIDAZINE
  申请人：PFIZER PROD INC

  公开号：WO2007138472A2

  公开（公告）日：2007-12-06

  [EN] The invention relates to compounds of the formula (I) or a pharmaceutically acceptable salt thereof, wherein R¹, R², R³ and R³
  [FR] La présente invention concerne des composés de formule (I) ou un de leurs sels pharmaceutiquement acceptable, dans laquelle R¹, R², R³ et R^3' sont tels que définis ici. L'invention concerne également des compositions pharmaceutiques contenant les composés de formule (I) et des procédés de traitement des affections hyperprolifératives chez un mammifère par l'administration des composés de formule (I).