3-(3-nitro-4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester | 1049103-22-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-nitro-4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 3-[3-nitro-4-(trifluoromethyl)phenyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylate
• CAS: 1049103-22-1
• 化学式: C₁₈H₁₉F₃N₄O₄
• 分子量: 412.368
• InChiKey: RAKKDTSYLJCMKR-UHFFFAOYSA-N

物化性质

• 沸点：
  560.7±50.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(3-nitro-4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester 、 巯基乙酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以67%的产率得到Tert-butyl 3-[3-(2-ethoxy-2-oxoethyl)sulfanyl-4-(trifluoromethyl)phenyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylate
  参考文献：
  名称：

  Thioether acetamides as P3 binding elements for tetrahydropyrido-pyrazole cathepsin S inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2010.01.103

文献信息

• 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。
• 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.