1-(4-bromophenylsulphonyl)-4-[1-(3-chloro-pyridin-4-yl)piperazin4-ylcarbonyl]piperazine

• 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-bromophenylsulphonyl)-4-[1-(3-chloro-pyridin-4-yl)piperazin4-ylcarbonyl]piperazine
• 英文别名: 1-(4-bromophenylsulphonyl)-4-[1-(3-chloro-4-pyridyl)piperazin4-ylcarbonyl]piperazine；[4-(4-bromophenyl)sulfonylpiperazin-1-yl]-[4-(3-chloropyridin-4-yl)piperazin-1-yl]methanone
• 化学式: C₂₀H₂₃BrClN₅O₃S
• 分子量: 528.857
• InChiKey: IQUUVFGAQRQZPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(4-bromophenylsulphonyl)-4-[1-(pyridin-4-yl)piperazin-4-ylcarbonyl]piperazine 在 N-氯代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 生成 1-(4-bromophenylsulphonyl)-4-[1-(3-chloro-pyridin-4-yl)piperazin4-ylcarbonyl]piperazine
  参考文献：
  名称：

  Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pKa

  摘要：

  Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase (OSC) was maintained after structural modification of the 4-piperidinopyridine OSC inhibitor series. These novel analogues with a much lower pK(a) range (5.8-6.7) gave potent oral inhibition of rat cholesterol biosynthesis (8 ED80 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00423-1

文献信息

• Heterocyclic compounds useful as oxido-squalene cyclase inhibitors
  申请人：Zeneca Limited

  公开号：US06440972B1

  公开（公告）日：2002-08-27

  This invention concerns heterocyclic derivatives of formula (I) which are useful in inhibiting oxido-squalene cyclase, processes for their preparation and pharmaceutical compositions containing them. The present invention is also concerned with heterocyclic derivatives capable of inhibiting cholesterol biosynthesis and hence the lowering cholesterol levels in blood plasma. The present invention also relates to methods of using such heterocyclic derivatives in diseases and medical conditions such as hypercholesterolemia and atherosclerosis.

  这项发明涉及式(I)的杂环衍生物，其在抑制氧化齿萜环化酶方面具有用途，以及其制备方法和含有它们的药物组合物。本发明还涉及能够抑制胆固醇生物合成并因此降低血浆胆固醇水平的杂环衍生物。本发明还涉及在高胆固醇血症和动脉粥样硬化等疾病和医疗状况中使用这种杂环衍生物的方法。
• HETEROCYCLIC COMPOUNDS USEFUL AS OXIDO-SQUALENE CYCLASE INHIBITORS
  申请人：ZENECA LIMITED

  公开号：EP0966460A1

  公开（公告）日：1999-12-29
• US6440972B1
  申请人：——

  公开号：US6440972B1

  公开（公告）日：2002-08-27
• [EN] HETEROCYCLIC COMPOUNDS USEFUL AS OXIDO-SQUALENE CYCLASE INHIBITORS<br/>[FR] COMPOSES HETEROCYCLIQUES UTILISES COMME INHIBITEURS DE L'OXYDO-SQUALENE CYCLASE
  申请人：ZENECA LIMITED

  公开号：WO1998035956A1

  公开（公告）日：1998-08-20

  (EN) This invention concerns heterocyclic derivatives of formula (I) which are useful in inhibiting oxido-squalene cyclase, processes for their preparation and pharmaceutical compositions containing them. The present invention is also concerned with heterocyclic derivatives capable of inhibiting cholesterol biosynthesis and hence in lowering cholesterol levels in blood plasma. The present invention also relates to methods of using such heterocyclic derivatives in diseases and medical conditions such as hypercholesterolemia and atherosclerosis.(FR) La présente invention concerne des dérivés hétérocycliques de la formule (I) qui sont utilisés pour inhiber l'oxydo-squalène cyclase, des procédés de préparation de ces derniers et des compositions pharmaceutiques les contenant. La présente invention se rapporte également à des dérivés hétérocycliques capables d'inhiber la biosynthèse du cholestérol et, par conséquent, de réduire les niveaux de cholestérol du plasma sanguin. La présente invention concerne enfin des procédés permettant d'utiliser ces dérivés hétérocycliques lors de maladies et d'états pathologiques tels que l'hypercholestérolémie et l'athérosclérose.
• Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pKa
  作者：George R Brown、Alan J Foubister、Michael C Johnson、Nicholas J Newcombe、David Waterson、Stuart L Wells

  DOI：10.1016/s0960-894x(01)00423-1

  日期：2001.8

  Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase (OSC) was maintained after structural modification of the 4-piperidinopyridine OSC inhibitor series. These novel analogues with a much lower pK(a) range (5.8-6.7) gave potent oral inhibition of rat cholesterol biosynthesis (8 ED80 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose. (C) 2001 Elsevier Science Ltd. All rights reserved.