1-[1-(3-{3-[3-(2-Amino-ethylsulfanyl)-4-trifluoromethyl-phenyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl)-piperidin-4-yl]-pyrrolidin-2-one | 1049094-71-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-[1-(3-{3-[3-(2-Amino-ethylsulfanyl)-4-trifluoromethyl-phenyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl)-piperidin-4-yl]-pyrrolidin-2-one
• 英文别名: 1-[1-[3-[3-[3-(2-aminoethylsulfanyl)-4-(trifluoromethyl)phenyl]-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]pyrrolidin-2-one
• CAS: 1049094-71-4
• 化学式: C₂₈H₃₉F₃N₆O₄S₂
• 分子量: 644.783
• InChiKey: XJZLUOSUAVPLLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1-[1-(3-{3-[3-(2-Amino-ethylsulfanyl)-4-trifluoromethyl-phenyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl)-piperidin-4-yl]-pyrrolidin-2-one 、 1-BOC-哌啶-3-羧酸 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-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-{2-[5-(1-{2-Hydroxy-3-[4-(2-oxo-pyrrolidin-1-yl)-piperidin-1-yl]-propyl}-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-trifluoromethyl-phenylsulfanyl]-ethylcarbamoyl}-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors: Part 1

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2010.01.108
• 作为产物：
  描述：

  {2-[5-(1-{2-hydroxy-3-[4-(2-oxo-pyrrolidin-1-yl)-piperidin-1-yl]-propyl}-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-trifluoromethyl-phenylsulfanyl]-ethyl}-carbamic acid tert-butyl ester 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-[1-(3-{3-[3-(2-Amino-ethylsulfanyl)-4-trifluoromethyl-phenyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl)-piperidin-4-yl]-pyrrolidin-2-one
  参考文献：
  名称：

  Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors: Part 1

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2010.01.108

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。
• [EN] TETRAHYDRO-PYRAZOLO-PYRIDINE THIOETHER MODULATORS OF CATHEPSIN S<br/>[FR] MODULATEURS DE LA CATHEPSINE S AU THIOÉTHER DE TÉTRAHYDRO-PYRAZOLO-PYRIDINE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2008100621A2

  公开（公告）日：2008-08-21

  [EN] 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.
  [FR] L'invention concerne des composés de thioéther de tétrahydro-pyrazolo-pyridine, qui sont utiles en tant que modulateurs de cathepsine S. De tels composés peuvent être utilisés dans des compositions pharmaceutiques et des procédés pour le traitement de maladies, de troubles et d'états provoqués par l'activité de la cathepsine S, tels que le psoriasis, la douleur, la sclérose en plaques, l'athérosclérose, et l'arthrite rhumatoïde.
• 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.