Tert-butyl 4-[3-(2-chloropyridin-4-yl)isoquinolin-1-yl]piperazine-1-carboxylate | 1239581-17-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Tert-butyl 4-[3-(2-chloropyridin-4-yl)isoquinolin-1-yl]piperazine-1-carboxylate
• CAS: 1239581-17-9
• 化学式: C₂₃H₂₅ClN₄O₂
• 分子量: 424.93
• InChiKey: RSXBELICLMTWMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[3-(2-chloropyridin-4-yl)isoquinolin-1-yl]piperazine-1-carboxylate 、 环己胺 在 potassium tert-butylate 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 生成
  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
• 作为产物：
  描述：

  1-chloro-3-(2-chloropyridin-4-yl)isoquinoline 、 N-Boc-哌嗪 以 N-甲基吡咯烷酮 为溶剂， 反应 0.75h， 以51%的产率得到Tert-butyl 4-[3-(2-chloropyridin-4-yl)isoquinolin-1-yl]piperazine-1-carboxylate
  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

• 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.