1-(4-bromophenylsulphonyl)-4-[1-(pyridin-4-yl)piperidin-4-ylcarbonyl]piperazine | 179050-10-3

• 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: 1-(4-bromophenylsulphonyl)-4-[1-(pyridin-4-yl)piperidin-4-ylcarbonyl]piperazine
• 英文别名: 1-(4-bromophenylsulphonyl)-4-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperazine；[4-(4-bromophenyl)sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone
• CAS: 179050-10-3
• 化学式: C₂₁H₂₅BrN₄O₃S
• 分子量: 493.424
• InChiKey: NTEVEFOEWIWAOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-bromophenylsulphonyl)-4-[1-(pyridin-4-yl)piperidin-4-ylcarbonyl]piperazine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 生成 [4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-(3'-bromo-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-methanone
  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
• 作为产物：
  描述：

  1-(4-pyridinyl)piperidin-4-yl carbonyl chloride 在 吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 1-(4-bromophenylsulphonyl)-4-[1-(pyridin-4-yl)piperidin-4-ylcarbonyl]piperazine
  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

• Pyridyl-and pyrimidyl-heterocyclic compounds inhibiting oxido squalene-cyclase
  申请人：Zeneca Limited

  公开号：US06335341B1

  公开（公告）日：2002-01-01

  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 treating or preventing diseases and medical conditions such as hypercholesterolemia, atherosclerosis and other medical conditions associated with elevated cholesterol levels. In formula (I): G is selected from CH or N; R1 is selected from hydrogen, halogeno, (1-6C)alkyl, halogeno(1-6C)alkyl, cyano, nitro, (1-6C)alkoxycarbonyl, and NR3R4 wherein R3 and R4 are independently selected from hydrogen and (1-6C)alkyl, and wherein up to 3 R1 groups may be present; T1 is selected from CH or N; T2 and T2 are independently selected from N and CR, wherein R is selected from hydrogen, hydroxyl and (C1-4)alkyl and wherein either ring containing T2 or T3 is optionally substituted with an oxo group; R2 is selected from hydrogen or (1-4C)alkyl; Q is selected from SO2, CO and CH2; AR is selected from a five or six-membered heterocycle containing up to 3 heteroatoms selected from nitrogen, oxygen and sulphur, phenyl, phenyl (2-6)alkenyl and naphthyl in which any Ar group is optionally substituted by one or more substituents selected from (1-6C)alkyl, halogeno, halogeno (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, cyano, (1-6C)alkylamido, nitro, NR3R4 wherein R3 and R4 are independently selected from hydrogen and (1-4C)alkyl; provided that both T2 and T3 are not N and that when T2 is CR then T1 is not CH.

  这项发明涉及对氧化齿萜环化酶具有抑制作用的杂环衍生物，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。本发明还涉及使用这种杂环衍生物治疗或预防高胆固醇血症、动脉粥样硬化和其他与胆固醇水平升高相关的疾病和医疗状况的方法。在式（I）中：G选择自CH或N；R1选择自氢、卤素、（1-6C）烷基、卤代（1-6C）烷基、氰基、硝基、（1-6C）氧代羰基和NR3R4，其中R3和R4独立选择自氢和（1-6C）烷基，且最多可存在3个R1基团；T1选择自CH或N；T2和T2独立选择自N和CR，其中R选择自氢、羟基和（C1-4）烷基，且含有T2或T3的任一环可选择性地被氧基取代；R2选择自氢或（1-4C）烷基；Q选择自SO2、CO和CH2；AR选择自含有最多3个异原子（氮、氧和硫）的五元或六元杂环、苯基、苯基（2-6）烯基和萘基，其中任何Ar基团可选择性地被一个或多个取代基取代，所述取代基选择自（1-6C）烷基、卤素、卤代（1-6C）烷基、（1-6C）氧基、（1-6C）氧代羰基、氰基、（1-6C）烷基氨基、硝基、NR3R4，其中R3和R4独立选择自氢和（1-4C）烷基；但要求T2和T3均不为N，且当T2为CR时，则T1不为CH。
• 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
• 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
• PYRIDYL- AND PYRIMIDYL-HETEROCYCLIC COMPOUNDS INHIBITING OXIDO SQUALENE-CYCLASE
  申请人：AstraZeneca UK Limited

  公开号：EP1000057A1

  公开（公告）日：2000-05-17
• US6335341B1
  申请人：——

  公开号：US6335341B1

  公开（公告）日：2002-01-01