[4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-(1-pyrimidin-4-yl-piperidin-4-yl)-methanone | 188526-95-6

• 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-Bromo-benzenesulfonyl)-piperazin-1-yl]-(1-pyrimidin-4-yl-piperidin-4-yl)-methanone
• 英文别名: [4-(4-bromophenyl)sulfonylpiperazin-1-yl]-(1-pyrimidin-4-ylpiperidin-4-yl)methanone
• CAS: 188526-95-6
• 化学式: C₂₀H₂₄BrN₅O₃S
• 分子量: 494.412
• InChiKey: VSGXABIFGUPLNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  95.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-(1-pyrimidin-4-yl-piperidin-4-yl)-methanone 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]-[1-(5-bromo-pyrimidin-4-yl)-piperidin-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-溴苯基磺酰基)哌嗪 在 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 41.0h， 生成 [4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-(1-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

• 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
• [EN] USE OF OXIDO-SQUALENE CYCLASE INHIBITORS TO LOWER BLOOD CHOLESTEROL<br/>[FR] UTILISATION D'INHIBITEURS D'OXYDO-SQUALENES CYCLASES AUX FINS D'ABAISSEMENT DU CHOLESTEROL SANGUIN
  申请人：——

  公开号：WO1997006802A1

  公开（公告）日：1997-02-27

  [EN] A compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein G, T<1>, T<2> and T<3> are selected from CH and N; provided that T<2> and T<3> are not both CH; A is selected from a direct bond and (1-4C)alkylene; X is selected from oxy, thio, sulphinyl, sulphonyl, carbonyl, carbonylamino, N-di-(1-6C)alkylcarbonylamino, sulphonamido, methylene, (1-4C)alkylmethylene and di-(1-6C)alkylmethylene, and when T<2> is CH, X may also be selected from aminosulphonyl and oxycarbonyl; and Q is selected from (5-7C)cycloalkyl, a heterocyclic moiety containing up to 4 heteroatoms selected from nitrogen, oxygen and sulphur; phenyl, naphthyl, phenyl(1-4C)alkyl and phenyl(2-6C)alkenyl; for the manufacture of a medicament for treating diseases or medical conditions in which an inhibition of oxido-squalene cyclase is desirable.
  [FR] On décrit un composé de la formule (I), ou un sel de celui-ci acceptable sur le plan pharmacologique. Dans cette formule G, T<1>, T<2> et T<3> représentent CH ou N, à condition que T<2> et T<3> ne représentent pas tous deux CH; A représente une liaison directe ou alkylène(C1-4); X est choisi dans le groupe constitué par oxy, thio, sulfinyle, sulfonyle, carbonyle, carbonylamino, N-dialkyl(C1-6)carbonylamino, sulfonamido, méthylène, alkyl(C1-4)méthylène et di-alkyl(C1-6)méthylène, et lorsque T<2> représente CH, X peut représenter aminosulfonyle ou oxycarbonyle; et Q représente cycloalkyle(C5-7), une fraction hétérocyclique contenant jusqu'à 4 hétéroatomes choisis parmi azote, oxygène et soufre; phényle, naphtyle, phényl-alkyle(C1-4) et phényl-alcényle(C2-6). Ce composé est destiné à la fabrication d'un médicament servant à traiter des maladies ou des états médicaux dans lesquels on souhaite inhiber les oxydo-squalènes cyclases.
• 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.
• 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.