5-methanesulfonyl-3-(3-nitro-4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine | 1049102-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-methanesulfonyl-3-(3-nitro-4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine
• 英文别名: 5-Methylsulfonyl-3-[3-nitro-4-(trifluoromethyl)phenyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine
• CAS: 1049102-98-8
• 化学式: C₁₄H₁₃F₃N₄O₄S
• 分子量: 390.343
• InChiKey: ZAJXAERFXFUTPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-methanesulfonyl-3-(3-nitro-4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine 、 2-巯基乙醇 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以100%的产率得到2-[5-(5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-trifluoromethyl-phenylsulfanyl]-ethanol
  参考文献：
  名称：

  TETRAHYDRO-PYRAZOLO-PYRIDINE THIOETHER MODULATORS OF CATHEPSIN S

  摘要：

  描述了四氢-吡唑-吡啶硫醚化合物，它们可用作猫hepsin S调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、疾病和病情的方法，这些疾病状态、疾病和病情是由猫hepsin S活性介导的，例如银屑病、疼痛、多发性硬化症、动脉硬化和类风湿性关节炎。

  公开号：

  US20090099157A1
• 作为产物：
  描述：

  3-硝基-4-(三氟甲基)苯甲酰氯 、 1-N-甲磺酰基-4-哌啶酮 在 吗啉 、 对甲苯磺酸 、 三乙胺 、 肼 作用下， 以 苯 、 二氯甲烷 、 乙醇 为溶剂， 反应 56.0h， 以38%的产率得到5-methanesulfonyl-3-(3-nitro-4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine
  参考文献：
  名称：

  TETRAHYDRO-PYRAZOLO-PYRIDINE THIOETHER MODULATORS OF CATHEPSIN S

  摘要：

  描述了四氢-吡唑-吡啶硫醚化合物，它们可用作猫hepsin S调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、疾病和病情的方法，这些疾病状态、疾病和病情是由猫hepsin S活性介导的，例如银屑病、疼痛、多发性硬化症、动脉硬化和类风湿性关节炎。

  公开号：

  US20090099157A1

文献信息

• Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors. Part 2: Modification of P3, P4, and P5 regions
  作者：John J.M. Wiener、Alvah T. Wickboldt、Danielle K. Wiener、Alice Lee-Dutra、James P. Edwards、Lars Karlsson、Steven Nguyen、Siquan Sun、Todd K. Jones、Cheryl A. Grice

  DOI：10.1016/j.bmcl.2010.01.104

  日期：2010.4

  A novel class of tetrahydropyrido-pyrazole thioether amines that display potency against human Cathepsin S have been previously reported. Here, further SAR investigations of the P3, P4, and P5 regions are described. In particular, 4-fluoropiperidine is identified as a competent P3 binding element when utilized in conjunction with a (S)-2-hydroxypropyl linker-containing P5 moiety and oxamide or sulfonamide P4 substitution. (C) 2010 Elsevier Ltd. All rights reserved.
• Thioether acetamides as P3 binding elements for tetrahydropyrido-pyrazole cathepsin S inhibitors
  作者：Danielle K. Wiener、Alice Lee-Dutra、Scott Bembenek、Steven Nguyen、Robin L. Thurmond、Siquan Sun、Lars Karlsson、Cheryl A. Grice、Todd K. Jones、James P. Edwards

  DOI：10.1016/j.bmcl.2010.01.103

  日期：2010.4

  A series of tetrahydropyrido-pyrazole cathepsin S (CatS) inhibitors with thioether acetamide functional groups were prepared with the goal of improving upon the cellular activity of amidoethylthioethers. This Letter describes altered amide connectivity, in conjunction with changes to other binding elements, resulting in improved potency, as well as increased knowledge of the relationship between this chemotype and human CatS activity. Published by Elsevier Ltd.
• Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors: Part 1
  作者：Alice Lee-Dutra、Danielle K. Wiener、Kristen L. Arienti、Jing Liu、Neelakandha Mani、Michael K. Ameriks、Frank U. Axe、Damara Gebauer、Pragnya J. Desai、Steven Nguyen、Mike Randal、Robin L. Thurmond、Siquan Sun、Lars Karlsson、James P. Edwards、Todd K. Jones、Cheryl A. Grice

  DOI：10.1016/j.bmcl.2010.01.108

  日期：2010.4

  A series of pyrazole-based thioethers were prepared and found to be potent cathepsin S inhibitors. A crystal structure of 13 suggests that the thioether moiety may bind to the S3 pocket of the enzyme. Additional optimization led to the discovery of aminoethylthioethers with improved enzymatic activity and submicromolar cellular potency. (C) 2010 Elsevier Ltd. All rights reserved.
• TETRAHYDRO-PYRAZOLO-PYRIDINE THIOETHER MODULATORS OF CATHEPSIN S
  申请人：Ameriks Michael K.

  公开号：US20090099157A1

  公开（公告）日：2009-04-16

  Tetrahydro-pyrazolo-pyridine thioether compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.

  描述了四氢-吡唑-吡啶硫醚化合物，它们可用作猫hepsin S调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、疾病和病情的方法，这些疾病状态、疾病和病情是由猫hepsin S活性介导的，例如银屑病、疼痛、多发性硬化症、动脉硬化和类风湿性关节炎。