N-((4-((2-chloro-5-(5-(methylsulfonyl)-1-(3-morpholin-4-ylpropyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)ethynyl)phenyl)methyl)-1-phenylethanamine | 1049810-66-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((4-((2-chloro-5-(5-(methylsulfonyl)-1-(3-morpholin-4-ylpropyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)ethynyl)phenyl)methyl)-1-phenylethanamine
• 英文别名: N-[[4-[2-[2-chloro-5-[5-methylsulfonyl-1-(3-morpholin-4-ylpropyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]phenyl]ethynyl]phenyl]methyl]-1-phenylethanamine
• CAS: 1049810-66-3
• 化学式: C₃₇H₄₂ClN₅O₃S
• 分子量: 672.291
• InChiKey: BBVCFWJIGUDZPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(4-chloro-3-iodo-phenyl)-5-methanesulfonyl-1-(3-morpholin-4-yl-propyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine 、 N-[(4-ethynylphenyl)methyl]-1-phenylethanamine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 N-((4-((2-chloro-5-(5-(methylsulfonyl)-1-(3-morpholin-4-ylpropyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)ethynyl)phenyl)methyl)-1-phenylethanamine
  参考文献：
  名称：

  Pyrazole-based arylalkyne cathepsin S inhibitors. Part II: Optimization of cellular potency

  摘要：

  Basic lipophilic substituents dramatically improved the cellular potency of a previously disclosed series of pyrazole-based arylalkyne cathepsin S inhibitors. The incorporation of substituted benzylamines in the para position of the arylalkyne maintained enzymatic activity (hCatS IC(50) = 80-420 nM) and imparted cellular potency (IC(50) = 0.8-4.0 mu M). Further refinement of the morpholine portion of the pharmacophore enabled the identification of bicyclic piperidines with enhanced affinity for CatS (IC(50) = 10-30 nM) and sub-micromolar cellular potency (JY Ii IC(50) = 200-720 nM). (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.013

文献信息

• CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
  申请人：Ameriks Michael K.

  公开号：US20080200454A1

  公开（公告）日：2008-08-21

  Carbon-linked tetrahydro-pyrazolo-pyridine 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.

  描述了与碳相连的四氢吡唑吡啶化合物，这些化合物可作为cathepsin 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、疾病和病况的方法，这些疾病状态、疾病和病况是由cathepsin S活性介导的，如银屑病、疼痛、多发性硬化症、动脉粥样硬化和类风湿性关节炎。
• [EN] CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S<br/>[FR] MODULATEURS DE CATHEPSINE S À LA TÉTRAHYDRO-PYRAZOLO-PYRIDINE LIÉS AU CARBONE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2008100618A2

  公开（公告）日：2008-08-21

  [EN] Carbon-linked tetrahydro-pyrazolo-pyridine 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 tétrahydro-pyrazolo-pyridine liés au carbone 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 multiple, l'athérosclérose, et l'arthrite rhumatoïde.