tert-butyl 4-(1-(benzyloxycarbonyl)piperidin-4-carbonyl)piperazin-1-carboxylate | 203520-02-9

• 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: tert-butyl 4-(1-(benzyloxycarbonyl)piperidin-4-carbonyl)piperazin-1-carboxylate
• 英文别名: 1-(tert-butoxycarbonyl)-4-[1-benzyloxycarbonylpiperidin-4-ylcarbonyl]piperazine；1-(tert-butoxycarbonyl)-4-[1-benzyloxycarbonyl-4-piperidylcarbonyl]piperazine；1-(tert-butoxycarbonyl)-4-[1-(benzyloxycarbonyl)-4-piperidylcarboyl]piperazine；tert-butyl 4-(1-phenylmethoxycarbonylpiperidine-4-carbonyl)piperazine-1-carboxylate
• CAS: 203520-02-9
• 化学式: C₂₃H₃₃N₃O₅
• mdl: MFCD06808757
• 分子量: 431.532
• InChiKey: QMOOUSLDZCWGSL-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：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.608
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(1-(benzyloxycarbonyl)piperidin-4-carbonyl)piperazin-1-carboxylate 在 palladium on activated charcoal 氢气 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 39.0h， 生成 [4-(4-Bromophenyl)sulfonylpiperazin-1-yl]-(1-pyridazin-4-ylpiperidin-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
• 作为产物：
  描述：

  氯甲酸苄酯 在 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 tert-butyl 4-(1-(benzyloxycarbonyl)piperidin-4-carbonyl)piperazin-1-carboxylate
  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.

  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。本发明还涉及对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：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。
• [EN] N-(3-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PHENYL)BENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE N-(3-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PHÉNYL)BENZAMIDE
  申请人：NOVARTIS AG

  公开号：WO2019186343A1

  公开（公告）日：2019-10-03

  The invention relates to compounds of the formula (I) (I) or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to use of the compounds in the treatment of disease.

  该发明涉及公式（I）的化合物或其药用可接受的盐，其中取代基如规范中定义；涉及制备该化合物的中间体，包括该化合物的药物组合物以及该化合物在治疗疾病中的用途。
• [EN] INDAZOLE BASED COMPOUNDS AND ASSOCIATED METHODS OF USE<br/>[FR] COMPOSÉS À BASE D'INDAZOLE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2022198112A1

  公开（公告）日：2022-09-22

  Bifunctional compounds, of formula PTM-L-CLM, where the CLM is of formulae al-a4, the PTM f formula PTM-IA and L is a ligand. These compounds act on several diseases via agonism on LRRK2 and cereblon E3 ubiquitin ligase.

  双功能化合物，其化学式为 PTM-L-CLM，其中 CLM 的化学式为 al-a4，PTM 的化学式为 PTM-IA，L 为配体。这些化合物通过在 LRRK2 和 cereblon E3 泛素连接酶上的激动作用，对多种疾病产生作用。
• [EN] MODULATORS OF BCL6 PROTEOLYSIS AND ASSOCIATED METHODS OF USE<br/>[FR] MODULATEURS DE PROTÉOLYSE BCL6 ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2022221673A1

  公开（公告）日：2022-10-20

  Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a cereblon ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本文描述了双功能化合物，其作为B细胞淋巴瘤6蛋白（BCL6；目标蛋白）调节剂而发挥作用。具体而言，本公开的双功能化合物在一端含有结合到各自E3泛素连接酶的小脑球蛋白配体，而在另一端含有结合到目标蛋白的基团，从而将目标蛋白置于泛素连接酶的近旁，以实现目标蛋白的降解（和抑制）。本公开的双功能化合物表现出与目标蛋白的降解/抑制相关的广泛的药理活性。使用本公开的化合物和组合物治疗或预防由目标蛋白的聚集或积累引起的疾病或障碍。