tert-butyl4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine-1-carboxylate | 1177559-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine-1-carboxylate
• 英文别名: 1,1-dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinecarboxylate；tert-butyl 4-[[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl]piperidine-1-carboxylate
• CAS: 1177559-55-5
• 化学式: C₂₃H₃₆BNO₄
• 分子量: 401.354
• InChiKey: YSCGOAWOBHWBDO-UHFFFAOYSA-N

物化性质

• 沸点：
  499.8±28.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine-1-carboxylate 、 N-[(3-bromo-4-methylphenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 1,1-dimethylethyl 4-[(5'-{[({6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-1-piperazinecarboxylate
  参考文献：
  名称：

  Dual Pharmacophores - PDE4-Muscarinic Antagonistics

  摘要：

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。

  公开号：

  US20090203657A1
• 作为产物：
  描述：

  3-溴苄溴 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium 10% on activated carbon 氢气 、 potassium acetate 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 3.08h， 生成 tert-butyl4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS
  [FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4

  摘要：

  本发明涉及式(I) - (VI)的新化合物，以及其药学上可接受的盐、药物组合物及其在治疗中的应用，例如作为磷酸二酯酶IV (PDE4)的抑制剂和肌碱乙酰胆碱受体 (mAChRs)的拮抗剂，用于治疗和/或预防呼吸道疾病，包括炎症性和/或过敏性疾病，如慢性阻塞性肺病（COPD）、哮喘、鼻炎（例如过敏性鼻炎）、特应性皮炎或银屑病。

  公开号：

  WO2009100169A1

文献信息

• Dual pharmacophores—PDE4-muscarinic antagonistics
  申请人：Glaxo Group Limited

  公开号：US08067408B2

  公开（公告）日：2011-11-29

  The present invention is directed to novel compounds of Formula (I), pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of/and or prophylaxis of respiratory diseases, including antiinflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.

  本发明涉及公式（I）的新化合物、制药组合物及其在治疗中的应用，例如作为磷酸二酯酶IV（PDE4）的抑制剂和肌肉型乙酰胆碱受体（mAChRs）的拮抗剂，在治疗和/或预防呼吸系统疾病中发挥作用，包括抗炎和/或过敏疾病，如慢性阻塞性肺疾病（COPD）、哮喘、鼻炎（如过敏性鼻炎）、特应性皮炎或银屑病。
• Design and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration
  作者：Matthew W. D. Perry、Karin Björhall、Britta Bonn、Johan Carlsson、Yunhua Chen、Anders Eriksson、Linda Fredlund、Hai’e Hao、Neil S. Holden、Kostas Karabelas、Helena Lindmark、Feifei Liu、Nils Pemberton、Jens Petersen、Sandra Rodrigo Blomqvist、Reed W. Smith、Tor Svensson、Ina Terstiege、Christian Tyrchan、Wenzhen Yang、Shuchun Zhao、Linda Öster

  DOI：10.1021/acs.jmedchem.7b00401

  日期：2017.6.22

  PI3K delta is a lipid kinase that is believed to be important in the migration and activation of cells of the immune system. Inhibition is hypothesized to provide a powerful yet selective immunomodulatory effect that may be beneficial for the treatment of conditions such as asthma or rheumatoid arthritis. In this work, we describe the identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation: The initially identified compound (13) had good potency and isoform selectivity but was not suitable for inhalation. Addition of basic substituents to a region of the molecule pointing to solvent was tolerated (enzyme inhibition pIC(50) > 9), and by careful manipulation, of the pK(a) and lipophilicity, we were able to discover compounds (20b, 20f) with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated.
• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。
• [EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS<br/>[FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2009100169A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.

  本发明涉及式(I) - (VI)的新化合物，以及其药学上可接受的盐、药物组合物及其在治疗中的应用，例如作为磷酸二酯酶IV (PDE4)的抑制剂和肌碱乙酰胆碱受体 (mAChRs)的拮抗剂，用于治疗和/或预防呼吸道疾病，包括炎症性和/或过敏性疾病，如慢性阻塞性肺病（COPD）、哮喘、鼻炎（例如过敏性鼻炎）、特应性皮炎或银屑病。