1-(4-Bromomethyl-phenyl)-piperidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-Bromomethyl-phenyl)-piperidin-2-one
• 英文别名: 1-[4-(Bromomethyl)phenyl]piperidin-2-one
• 化学式: C₁₂H₁₄BrNO
• 分子量: 268.153
• InChiKey: AKZOVVRKIDJRQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-Bromomethyl-phenyl)-piperidin-2-one 在 dimethyl sulfide borane 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (6S)-2-nitro-6-[[4-(1-piperidyl)phenyl]methoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  Synthesis and evaluation of pretomanid (PA-824) oxazolidinone hybrids

  摘要：

  Pretomanid (PA-824) is an important nitroimidazole antitubercular agent in late stage clinical trials. However, pretomanid is limited by poor solubility and high protein binding, which presents opportunities for improvement in its physiochemical properties. Conversely, the oxazolidinone linezolid has excellent physicochemical properties and has recently shown impressive activity for the treatment of drug resistant tuberculosis. In this study we explore if incorporation of the outer ring elements found in first and second generation oxazolidinones into the nitroimidazole core of pretomanid can be used to improve its physicochemical and antitubercular properties. The synthesis of pretomanid outer oxazolidinone ring hybrids was successfully performed producing hybrids that maintained antitubercular activity and had improved in vitro physicochemical properties. Three lead compounds were identified and evaluated in a chronic model of tuberculosis infection in mice. However, the compounds lacked efficacy suggesting that portions of PA-824 tail not found in the hybrid molecules are required for in vivo efficacy. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.002
• 作为产物：
  描述：

  1-溴-4-叔丁基二甲基硅烷氧甲基苯 在 copper(l) iodide 、 四溴化碳 、 四丁基氟化铵 、 potassium carbonate 、 三苯基膦 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 26.0h， 生成 1-(4-Bromomethyl-phenyl)-piperidin-2-one
  参考文献：
  名称：

  Synthesis and evaluation of pretomanid (PA-824) oxazolidinone hybrids

  摘要：

  Pretomanid (PA-824) is an important nitroimidazole antitubercular agent in late stage clinical trials. However, pretomanid is limited by poor solubility and high protein binding, which presents opportunities for improvement in its physiochemical properties. Conversely, the oxazolidinone linezolid has excellent physicochemical properties and has recently shown impressive activity for the treatment of drug resistant tuberculosis. In this study we explore if incorporation of the outer ring elements found in first and second generation oxazolidinones into the nitroimidazole core of pretomanid can be used to improve its physicochemical and antitubercular properties. The synthesis of pretomanid outer oxazolidinone ring hybrids was successfully performed producing hybrids that maintained antitubercular activity and had improved in vitro physicochemical properties. Three lead compounds were identified and evaluated in a chronic model of tuberculosis infection in mice. However, the compounds lacked efficacy suggesting that portions of PA-824 tail not found in the hybrid molecules are required for in vivo efficacy. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.002

文献信息

• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05939439A1

  公开（公告）日：1999-08-17

  The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

  本发明涉及抑制法尼基-蛋白转移酶（FTase）和致癌基因蛋白Ras法尼酰化的化合物。该发明还涉及含有本发明化合物的化疗组合物以及抑制法尼基-蛋白转移酶和致癌基因蛋白Ras法尼酰化的方法。
• US5939439A
  申请人：——

  公开号：US5939439A

  公开（公告）日：1999-08-17
• US6077853A
  申请人：——

  公开号：US6077853A

  公开（公告）日：2000-06-20
• Synthesis and evaluation of pretomanid (PA-824) oxazolidinone hybrids
  作者：Rakesh、David F. Bruhn、Michael S. Scherman、Aman P. Singh、Lei Yang、Jiuyu Liu、Anne J. Lenaerts、Richard E. Lee

  DOI：10.1016/j.bmcl.2015.12.002

  日期：2016.1

  Pretomanid (PA-824) is an important nitroimidazole antitubercular agent in late stage clinical trials. However, pretomanid is limited by poor solubility and high protein binding, which presents opportunities for improvement in its physiochemical properties. Conversely, the oxazolidinone linezolid has excellent physicochemical properties and has recently shown impressive activity for the treatment of drug resistant tuberculosis. In this study we explore if incorporation of the outer ring elements found in first and second generation oxazolidinones into the nitroimidazole core of pretomanid can be used to improve its physicochemical and antitubercular properties. The synthesis of pretomanid outer oxazolidinone ring hybrids was successfully performed producing hybrids that maintained antitubercular activity and had improved in vitro physicochemical properties. Three lead compounds were identified and evaluated in a chronic model of tuberculosis infection in mice. However, the compounds lacked efficacy suggesting that portions of PA-824 tail not found in the hybrid molecules are required for in vivo efficacy. (C) 2015 Elsevier Ltd. All rights reserved.