1-{3-[2-(tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic acid isobutylamide | 1071133-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-{3-[2-(tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic acid isobutylamide
• 英文别名: N-(2-methylpropyl)-1-[3-[2-(oxan-4-ylamino)pyridin-4-yl]-2,6-naphthyridin-1-yl]piperidine-4-carboxamide
• CAS: 1071133-37-3
• 化学式: C₂₈H₃₆N₆O₂
• 分子量: 488.633
• InChiKey: XJHFJRVRIHZMMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氨基四氢吡喃 、 1-[3-(2-chloropyridin-4-yl)-[2,6]naphthyridin-1-yl]piperidine-4-carboxylic acid isobutylamide 在 palladium⁽⁰⁾bis(tri-tert-butylphosphine) 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.5h， 生成 1-{3-[2-(tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic acid isobutylamide
  参考文献：
  名称：

  Identification of Orally Available Naphthyridine Protein Kinase D Inhibitors

  摘要：

  A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was proposed as a potential antihypertrophic mechanism with application as a heart failure therapy. As PKC was previously identified as the immediate upstream activator of PKD, PKD vs PKC selectivity was essential to understand the effect of PKD inhibition in models of cardiac hypertrophy and heart failure. The present study describes the modification of the HTS hit to a series of prototype pan-PKD inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds inhibited PKD activity in vitro, in cells, and in vivo following oral administration. Their effects on heart morphology and function are discussed herein.

  DOI：

  10.1021/jm100075z

文献信息

• ORGANIC COMPOUNDS
  申请人：Dobler Markus Rolf

  公开号：US20120142685A1

  公开（公告）日：2012-06-07

  The present invention provides a compound formula I: (formula I) said compound is inhibitor of selective subset of kinases belonging to the AGC or calmodulin kinase family, such as for example MARK1/2/3, PKD-1/2/3, PKN-1/2, CDK-9, CaMKII, ROCK-I/II, inhibitors of histone deacetylase (HDAC) phosphorylation, or inhibitors of other kinases. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一个化合物公式I：（公式I），该化合物是AGC或钙调素激酶家族的选择性亚集的抑制剂，例如MARK1/2/3，PKD-1/2/3，PKN-1/2，CDK-9，CaMKII，ROCK-I/II，组蛋白去乙酰化酶（HDAC）磷酸化抑制剂，或其他激酶的抑制剂。最后，本发明还提供了一种制药组合物。
• [2,6]NAPHTHYRIDINES USEFUL AS PROTEIN KINASE INHIBITORS
  申请人：Novartis AG

  公开号：EP2144909B1

  公开（公告）日：2011-03-23
• [EN] [2, 6] NAPHTHYRIDINES USEFUL AS PROTEIN KINASE INHIBITORS<br/>[FR] [2,6]NAPHTHYRIDINES UTILES EN TANT QU'INHIBITEURS DES PROTEINES KINASES
  申请人：NOVARTIS AG

  公开号：WO2008122615A1

  公开（公告）日：2008-10-16

  [EN] The present invention provides a compound of formula I: (formula I) said compound is inhibitor of selective subset of kinases belonging to the AGC or calmodulin kinase family, such as for example MARK1/2/3, PKD-1/2/3, PKN-1/2, CDK-9, CaMKII, ROCK-I/II, inhibitors of histone deacetylase (HDAC) phosphorylation, or inhibitors of other kinases. Finally, the present invention also provides a pharmaceutical composition.
  [FR] L'invention concerne un composés de formule I : (formule I), utile en tant qu'inhibiteur d'un sous-ensemble sélectif de kinases appartenant à la famille des kinases AGC ou calmoduline, telles que MARK1/2/3, PKD-1/2/3, PKN-1/2, CDK-9, CaMKII, ROCK-I/II, inhibiteurs de la phosphorylation d'histone désacétylase (HDAC) ou inhibiteurs d'autres kinases. L'invention concerne également une composition pharmaceutique associée.
• Identification of Orally Available Naphthyridine Protein Kinase D Inhibitors
  作者：Erik L. Meredith、Ophelia Ardayfio、Kimberly Beattie、Markus R. Dobler、Istvan Enyedy、Christoph Gaul、Vinayak Hosagrahara、Charles Jewell、Keith Koch、Wendy Lee、HansJoerg Lehmann、Timothy A. McKinsey、Karl Miranda、Nikos Pagratis、Margaret Pancost、Anup Patnaik、Dillon Phan、Craig Plato、Ming Qian、Vasumathy Rajaraman、Chang Rao、Olga Rozhitskaya、Thomas Ruppen、Jie Shi、Sarah J. Siska、Clayton Springer、Maurice van Eis、Richard B. Vega、Anette von Matt、Lihua Yang、Taeyoung Yoon、Ji-Hu Zhang、Na Zhu、Lauren G. Monovich

  DOI：10.1021/jm100075z

  日期：2010.8.12

  A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was proposed as a potential antihypertrophic mechanism with application as a heart failure therapy. As PKC was previously identified as the immediate upstream activator of PKD, PKD vs PKC selectivity was essential to understand the effect of PKD inhibition in models of cardiac hypertrophy and heart failure. The present study describes the modification of the HTS hit to a series of prototype pan-PKD inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds inhibited PKD activity in vitro, in cells, and in vivo following oral administration. Their effects on heart morphology and function are discussed herein.