3-(4-Chloro-3-iodo-phenyl)-1-(3-morpholin-4-yl-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester | 1049809-53-1

• 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-(4-Chloro-3-iodo-phenyl)-1-(3-morpholin-4-yl-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 3-(4-chloro-3-iodophenyl)-1-(3-morpholin-4-ylpropyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate
• CAS: 1049809-53-1
• 化学式: C₂₄H₃₂ClIN₄O₃
• 分子量: 586.901
• InChiKey: QLVBRISOFFTOOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  59.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(4-Chloro-3-iodo-phenyl)-1-(3-morpholin-4-yl-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-(4-chloro-benzyl)-N-(4-{2-chloro-5-[1-(3-morpholin-4-yl-propyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]phenylethynyl}-benzyl)-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  Pyrazole-based arylalkyne Cathepsin S inhibitors. Part III: Modification of P4 region

  摘要：

  Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.014
• 作为产物：
  描述：

  3-(4-Chloro-3-iodo-phenyl)-1-(3-hydroxy-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester 在 戴斯-马丁氧化剂 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 3-(4-Chloro-3-iodo-phenyl)-1-(3-morpholin-4-yl-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pyrazole-based arylalkyne Cathepsin S inhibitors. Part III: Modification of P4 region

  摘要：

  Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.014

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。
• Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements
  作者：Michael K. Ameriks、Frank U. Axe、Scott D. Bembenek、James P. Edwards、Yin Gu、Lars Karlsson、Mike Randal、Siquan Sun、Robin L. Thurmond、Jian Zhu

  DOI：10.1016/j.bmcl.2009.09.014

  日期：2009.11

  A crystal structure of 1 bound to a Cys25Ser mutant of cathepsin S helped to elucidate the binding mode of a previously disclosed series of pyrazole-based CatS inhibitors and facilitated the design of a new class of arylalkyne analogs. Optimization of the alkyne and tetrahydropyridine portions of the pharmacophore provided potent CatS inhibitors (IC(50) = 40-300 nM), and an X-ray structure of 32 revealed that the arylalkyne moiety binds in the S1 pocket of the enzyme. (c) 2009 Elsevier Ltd. All rights reserved.