1-[4-Chlorophenylsulfonyl]-4-[4-(4-methylpiperazin-1-yl)phenylmethyl]-piperazine | 1043508-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[4-Chlorophenylsulfonyl]-4-[4-(4-methylpiperazin-1-yl)phenylmethyl]-piperazine
• 英文别名: 1-[4-[[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]methyl]phenyl]-4-methylpiperazine
• CAS: 1043508-13-9
• 化学式: C₂₂H₂₉ClN₄O₂S
• 分子量: 449.017
• InChiKey: GFLWOSXFPVPSKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[(4-(4-methyl-piperazin-1-yl)phenyl)methyl]-piperazine 、 4-氯苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以82%的产率得到1-[4-Chlorophenylsulfonyl]-4-[4-(4-methylpiperazin-1-yl)phenylmethyl]-piperazine
  参考文献：
  名称：

  Design and evaluation of a novel series of 2,3-oxidosqualene cyclase inhibitors with low systemic exposure, relationship between pharmacokinetic properties and ocular toxicity

  摘要：

  We describe the discovery of novel potent inhibitors of 2,3-oxidosqualene: lanosterol cyclase inhibitors (OSCi) from a focused pharmacophore-based screen. Optimization of the most tractable hits gave a series of compounds showing inhibition of cholesterol biosynthesis at 2 mg/kg in the rat with distinct pharmacokinetic profiles. Two compounds were selected for toxicological study in the rat for 21 days in order to test the hypothesis that low systemic exposure could be used as a strategy to avoid the ocular side effects previously described with OSCi. We demonstrate that for this series of inhibitors, a reduction of systemic exposure is not sufficient to circumvent cataract liabilities. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.04.034

文献信息

• Design and evaluation of a novel series of 2,3-oxidosqualene cyclase inhibitors with low systemic exposure, relationship between pharmacokinetic properties and ocular toxicity
  作者：Marie-Hélène Fouchet、Frédéric Donche、Christelle Martin、Anne Bouillot、Christophe Junot、Anne-Bénédicte Boullay、Florent Potvain、Sylvie Demaria Magny、Hervé Coste、Max Walker、Marc Issandou、Nérina Dodic

  DOI：10.1016/j.bmc.2008.04.034

  日期：2008.6

  We describe the discovery of novel potent inhibitors of 2,3-oxidosqualene: lanosterol cyclase inhibitors (OSCi) from a focused pharmacophore-based screen. Optimization of the most tractable hits gave a series of compounds showing inhibition of cholesterol biosynthesis at 2 mg/kg in the rat with distinct pharmacokinetic profiles. Two compounds were selected for toxicological study in the rat for 21 days in order to test the hypothesis that low systemic exposure could be used as a strategy to avoid the ocular side effects previously described with OSCi. We demonstrate that for this series of inhibitors, a reduction of systemic exposure is not sufficient to circumvent cataract liabilities. (C) 2008 Elsevier Ltd. All rights reserved.