1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid | 1267425-40-0

• 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: 1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid
• 英文别名: 1-cyclopropyl-2-oxopyridine-3-carboxylic acid
• CAS: 1267425-40-0
• 化学式: C₉H₉NO₃
• 分子量: 179.175
• InChiKey: RGSANPKXHNPTPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 在 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-) 、 lithium chloride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl 4-(5-(1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxamido)-6-(2-hydroxypropan-2-yl)-2H-indazol-2-yl)[1,4’-bipiperidine]-1’-carboxylate
  参考文献：
  名称：

  [EN] DEGRADATION OF IRAK4 BY CONJUGATION OF IRAK4 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE
  [FR] DÉGRADATION D'IRAK4 PAR CONJUGAISON D'INHIBITEURS D'IRAK4 AVEC UN LIGAND DE LIGASE E3 ET PROCÉDÉS D'UTILISATION

  摘要：

  Disclosed herein are novel bifunctional compounds formed by conjugating IRAK4 inhibitor moieties with E3 ligase ligand moieties, which function to recruit targeted proteins to E3 ubiquitin ligase for degradation, and methods of preparation and uses thereof.

  公开号：

  WO2023237049A1
• 作为产物：
  描述：

  ethyl 1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以46%的产率得到1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid
  参考文献：
  名称：

  [EN] ISOINDOLINONE DERIVATIVES AS IRAK4 MODULATORS
  [FR] DÉRIVÉS D'ISOINDOLINONE UTILISÉS EN TANT QUE MODULATEURS D'IRAK4

  摘要：

  本文描述了公式（0）的化合物，以及其立体异构体和药用可接受的盐，以及作为白细胞介素-1受体相关激酶（IRAK4）抑制剂的使用方法。

  公开号：

  WO2018234342A1

文献信息

• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES DE CEUX-CI POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2020200899A1

  公开（公告）日：2020-10-08

  The present invention discloses compounds according to Formula I: Wherein R1, R2, R5 and Cy are as defined herein. The present invention relates to compounds, methods for the production of said compounds, pharmaceutical compositions comprising said compounds and methods for the prophylaxis and/or treatment of inflammatory diseases, autoimmune diseases, pain, fibrosis and/or proliferative diseases by administering said compounds.

  本发明公开了根据以下式I的化合物：其中R1、R2、R5和Cy如本文所定义。本发明涉及化合物、制备该化合物的方法、包括该化合物的药物组合物，以及通过给予该化合物来预防和/或治疗炎症性疾病、自身免疫疾病、疼痛、纤维化和/或增殖性疾病的方法。
• IRAK4 modulators
  申请人：Genentech, Inc.

  公开号：US10899772B2

  公开（公告）日：2021-01-26

  Compounds of Formula 0, and stereoisomers and pharmaceutically acceptable salts thereof, as well as methods of use as Interleukin-1 Receptor Associated Kinase (IRAK4) inhibitors are described herein.

  本文描述了式 0 的化合物及其立体异构体和药学上可接受的盐，以及作为白介素-1 受体相关激酶（IRAK4）抑制剂的使用方法。
• Discovery of Pyrrolopyridine−Pyridone Based Inhibitors of Met Kinase: Synthesis, X-ray Crystallographic Analysis, and Biological Activities
  作者：Kyoung Soon Kim、Liping Zhang、Robert Schmidt、Zhen-Wei Cai、Donna Wei、David K. Williams、Louis J. Lombardo、George L. Trainor、Dianlin Xie、Yaquan Zhang、Yongmi An、John S. Sack、John S. Tokarski、Celia Darienzo、Amrita Kamath、Punit Marathe、Yueping Zhang、Jonathan Lippy、Robert Jeyaseelan、Barri Wautlet、Benjamin Henley、Johnni Gullo-Brown、Veeraswamy Manne、John T. Hunt、Joseph Fargnoli、Robert M. Borzilleri

  DOI：10.1021/jm800476q

  日期：2008.9.11

  Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC(50) value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors Such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent anti proliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC(50) values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTI-16 human gastric carcinoma xenograft model.
• ISOINDOLINONE DERIVATIVES AS IRAK4 MODULATORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3642201A1

  公开（公告）日：2020-04-29
• NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  申请人：Galapagos N.V.

  公开号：EP3947377A1

  公开（公告）日：2022-02-09