4-[[4-[(4-Bromophenyl)sulfonyl]-1-piperazinyl]carbonyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester | 188527-18-6

• 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-[(4-Bromophenyl)sulfonyl]-1-piperazinyl]carbonyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl 4-[4-(4-bromophenyl)sulfonylpiperazine-1-carbonyl]piperidine-1-carboxylate
• CAS: 188527-18-6
• 化学式: C₂₁H₃₀BrN₃O₅S
• 分子量: 516.456
• InChiKey: ORBYTRVMSCIQAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  95.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[[4-[(4-Bromophenyl)sulfonyl]-1-piperazinyl]carbonyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester 在 三氟乙酸 作用下， 反应 1.0h， 以57%的产率得到1-(4-bromophenylsulphonyl)-4-(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
• 作为产物：
  描述：

  1-叔丁氧羰基-4-哌啶甲酸琥珀酰亚胺酯 、 1-(4-溴苯基磺酰基)哌嗪 以 二氯甲烷 为溶剂， 反应 40.0h， 以75%的产率得到4-[[4-[(4-Bromophenyl)sulfonyl]-1-piperazinyl]carbonyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester
  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：EP0925286A1

  公开（公告）日：1999-06-30
• US6093718A
  申请人：——

  公开号：US6093718A

  公开（公告）日：2000-07-25
• [EN] SUBSTITUTED PYRIMIDINE DERIVATIVES AND THEIR PHARMACEUTICAL USE<br/>[FR] DERIVES DE PYRIMIDINE SUBSTITUEE ET LEUR USAGE PHARMACEUTIQUE
  申请人：ZENECA LIMITED

  公开号：WO1998006705A1

  公开（公告）日：1998-02-19

  (EN) 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.(FR) La présente invention concerne des dérivés hétérocycliques permettant d'inhiber une oxydo-squalène cyclase, des procédés destinés à leur préparation, et des compositions pharmaceutiques contenant ces dérivés. La présente invention concerne également des dérivés hétérocycliques capables d'inhiber la biosynthèse du cholestérol et donc de réduire le taux de cholestérol dans le plasma sanguin. La présente invention concerne enfin des procédés d'utilisation de tels dérivés hétérocycliques pour des affections et des troubles médicaux tels que l'hypercholestérolémie et l'athérosclérose.
• A Novel Series of 4-Piperidinopyridine and 4-Piperidinopyrimidine Inhibitors of 2,3-Oxidosqualene Cyclase−Lanosterol Synthase
  作者：George R. Brown、David M. Hollinshead、Elaine S. E. Stokes、David Waterson、David S. Clarke、Alan J. Foubister、Steven C. Glossop、Fergus McTaggart、Donald J. Mirrlees、Graham J. Smith、Robin Wood

  DOI：10.1021/jm000139k

  日期：2000.12.1

  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.