3-methyl-4-nitro-1-(oxetan-3-yl)-1H-pyrazole | 1374830-15-5

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 3-methyl-4-nitro-1-(oxetan-3-yl)-1H-pyrazole
• 英文别名: 3-Methyl-4-nitro-1-(oxetan-3-yl)pyrazole
• CAS: 1374830-15-5
• 化学式: C₇H₉N₃O₃
• 分子量: 183.167
• InChiKey: WVSDSCOEXPOMNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methyl-4-nitro-1-(oxetan-3-yl)-1H-pyrazole 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以90%的产率得到3-methyl-1-(oxetan-3-yl)-1H-pyrazol-4-amine
  参考文献：
  名称：

  [EN] INHIBITORS
  [FR] INHIBITEURS

  摘要：

  这项发明涉及式(I)的化合物。该发明还涉及制备式(I)化合物的方法，含有该化合物的药物或组合物，或者使用该化合物治疗增殖性疾病，如癌症的方法。

  公开号：

  WO2015123722A1
• 作为产物：
  描述：

  3-溴环氧丁烷 、 3-甲基-4-硝基吡唑 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 144.0h， 以82%的产率得到3-methyl-4-nitro-1-(oxetan-3-yl)-1H-pyrazole
  参考文献：
  名称：

  [EN] INHIBITORS
  [FR] INHIBITEURS

  摘要：

  这项发明涉及式(I)的化合物。该发明还涉及制备式(I)化合物的方法，含有该化合物的药物或组合物，或者使用该化合物治疗增殖性疾病，如癌症的方法。

  公开号：

  WO2015123722A1

文献信息

• [EN] COMPOUND, COMPOSITIONS, AND METHODS<br/>[FR] COMPOSÉS, COMPOSITIONS, ET PROCÉDÉS
  申请人：DENALI THERAPEUTICS INC

  公开号：WO2017087905A1

  公开（公告）日：2017-05-26

  Compounds having activity as LRRK2 inhibitors are disclosed. The compounds are of formula (I) including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  披露了具有LRRK2抑制剂活性的化合物。这些化合物具有公式(I)，包括立体异构体、互变异构体、药物可接受的盐和前药。还披露了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。
• [EN] PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS<br/>[FR] DÉRIVÉS DE PYRAZOLE AMINOPYRIMIDINE EN TANT QUE MODULATEURS DU LRRK2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012062783A1

  公开（公告）日：2012-05-18

  Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

  化合物的结构式（I）或其药用盐，其中X，R1，R2，R3，R4和R5如本文所定义。还公开了制备这些化合物的方法，并将这些化合物用于治疗与LRRK2受体相关的疾病，如帕金森病。
• PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
  申请人：Baker-Glenn Charles

  公开号：US20120157427A1

  公开（公告）日：2012-06-21

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein X, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

  化合物I的公式为：或其药学上可接受的盐，其中X，R1，R2，R3，R4和R5如本文所定义。还公开了制备该化合物的方法以及使用该化合物治疗与LRRK2受体相关的疾病，如帕金森病的方法。
• Compound, compositions, and methods
  申请人：Denali Therapeutics Inc.

  公开号：US11214565B2

  公开（公告）日：2022-01-04

  Compounds having activity as LRRK2 inhibitors are disclosed. The compounds are of formula (I) including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds are also disclosed.

  本发明公开了具有 LRRK2 抑制剂活性的化合物。这些化合物为式（I）化合物，包括其立体异构体、同系物、药学上可接受的盐和原药。还公开了与制备和使用此类化合物相关的方法，以及包含此类化合物的药物组合物。
• Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors
  作者：Anthony A. Estrada、Bryan K. Chan、Charles Baker-Glenn、Alan Beresford、Daniel J. Burdick、Mark Chambers、Huifen Chen、Sara L. Dominguez、Jennafer Dotson、Jason Drummond、Michael Flagella、Reina Fuji、Andrew Gill、Jason Halladay、Seth F. Harris、Timothy P. Heffron、Tracy Kleinheinz、Donna W. Lee、Claire E. Le Pichon、Xingrong Liu、Joseph P. Lyssikatos、Andrew D. Medhurst、John G. Moffat、Kevin Nash、Kimberly Scearce-Levie、Zejuan Sheng、Daniel G. Shore、Susan Wong、Shuo Zhang、Xiaolin Zhang、Haitao Zhu、Zachary K. Sweeney

  DOI：10.1021/jm401654j

  日期：2014.2.13

  Leucine-rich repeat kinase 2 (LRRK2) has drawn significant interest in the neuroscience research community because it is one of the most compelling targets for a potential disease-modifying Parkinson's disease therapy. Herein, we disclose structurally diverse small molecule inhibitors suitable for assessing the implications of sustained in vivo LARK2 inhibition. Using previously reported aminopyrazole 2 as a lead molecule, we were able to engineer structural modifications in the solvent-exposed region of the ATP-binding site that significantly improve human hepatocyte stability, rat free brain exposure, and CYP inhibition and induction liabilities. Disciplined application of established optimal CNS design parameters culminated in the rapid identification of GNE-0877 (11) and GNE-9605 (20) as highly potent and selective LRRK2 inhibitors. The demonstrated metabolic stability, brain penetration across multiple species, and selectivity of these inhibitors support their use in preclinical efficacy and safety studies.