3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde | 850697-75-5

• 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-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde
• CAS: 850697-75-5
• 化学式: C₁₆H₁₈BrN₃O₃S
• 分子量: 412.307
• InChiKey: UOLGLZNCYPPFDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.27
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde 、 4-(2-酮基-3-甲基-1-苯并咪唑基)哌啶 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045
• 作为产物：
  描述：

  3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-1-ol 在 戴斯-马丁氧化剂 作用下， 生成 3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045

文献信息

• The SAR of 4-substituted (6,6-bicyclic) piperidine cathepsin S inhibitors
  作者：Cheryl A. Grice、Kevin Tays、Haripada Khatuya、Darin J. Gustin、Christopher R. Butler、Jianmei Wei、Clark A. Sehon、Siquan Sun、Yin Gu、Wen Jiang、Robin L. Thurmond、Lars Karlsson、James P. Edwards

  DOI：10.1016/j.bmcl.2006.01.038

  日期：2006.4

  A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacements for the 4-aryl piperazine resulted in the identification of potentially useful CatS inhibitors with enzymatic and Cellular activity similar to that of JNJ 10329670 as disclosed in a previous publication. (C) 2006 Elsevier Ltd. All rights reserved.