[4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-[1-(2-methyl-pyrimidin-4-yl)-piperidin-4-yl]-methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-[1-(2-methyl-pyrimidin-4-yl)-piperidin-4-yl]-methanone
• 英文别名: [4-(4-bromophenyl)sulfonylpiperazin-1-yl]-[1-(2-methylpyrimidin-4-yl)piperidin-4-yl]methanone
• 化学式: C₂₁H₂₆BrN₅O₃S
• 分子量: 508.439
• InChiKey: UKYGMIASKCNKIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  95.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(4-溴苯基磺酰基)哌嗪 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 57.0h， 生成 [4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-[1-(2-methyl-pyrimidin-4-yl)-piperidin-4-yl]-methanone
  参考文献：
  名称：

  A Novel Series of 4-Piperidinopyridine and 4-Piperidinopyrimidine Inhibitors of 2,3-Oxidosqualene Cyclase−Lanosterol Synthase

  摘要：

  A novel series of 4-piperidinopyridines and 4-piperidinopyrimidines showed potent and selective inhibition of rat 2,3-oxidosqualene cyclase-lanosterol synthase (OSC) (e.g. 26 IC50 rat = 398 +/- 25 nM, human = 112 +/- 25 nM) and gave selective oral inhibition of rat cholesterol biosynthesis (26 ED80 = 1.2 +/- 0.3 mg/kg, n = 5; HMGCoA reductase inhibitor simvastatin, ED80 = 1.2 +/- 0.3 mg/kg, n = 5). The piperidinopyrimidine OSC inhibitors have a significantly lower pK(a) than the corresponding pyridine or the previously reported quinuclidine OSC inhibitor series. This indicates that other novel OSC inhibitors may be found in analogues of this series across a broader pK(a) range (6.0-9.0). These series may yield novel hypocholesterolemic agents for the treatment of cardiovascular disease.

  DOI：

  10.1021/jm000139k

文献信息

• Substituted pyrimidine derivatives and their pharmaceutical use
  申请人：Zeneca Limited

  公开号：US06093718A1

  公开（公告）日：2000-07-25

  This invention concerns heterocyclic derivatives 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.

  本发明涉及杂环衍生物，其在抑制氧化齐墨酰基环化酶方面具有用途，以及制备它们的过程和含有它们的制药组合物。本发明还涉及能够抑制胆固醇生物合成并因此降低血浆中胆固醇水平的杂环衍生物。本发明还涉及在疾病和医疗条件（如高胆固醇血症和动脉硬化）中使用这种杂环衍生物的方法。
• USE OF OXIDO-SQUALENE CYCLASE INHIBITORS TO LOWER BLOOD CHOLESTEROL
  申请人：ZENECA LIMITED

  公开号：EP0844877A1

  公开（公告）日：1998-06-03
• SUBSTITUTED PYRIMIDINE DERIVATIVES AND THEIR PHARMACEUTICAL USE
  申请人：AstraZeneca AB

  公开号：EP0925286B1

  公开（公告）日：2003-01-02
• US6093718A
  申请人：——

  公开号：US6093718A

  公开（公告）日：2000-07-25
• US6090813A
  申请人：——

  公开号：US6090813A

  公开（公告）日：2000-07-18