N4-(piperidin-4-ylmethyl)-N6-(pyridin-3-yl)pyrimidine-4,6-diamine | 1351533-42-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N4-(piperidin-4-ylmethyl)-N6-(pyridin-3-yl)pyrimidine-4,6-diamine
• 英文别名: 6-N-(piperidin-4-ylmethyl)-4-N-pyridin-3-ylpyrimidine-4,6-diamine
• CAS: 1351533-42-0
• 化学式: C₁₅H₂₀N₆
• 分子量: 284.364
• InChiKey: RWQUDTGRBAGNSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74.8
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氨基吡啶 在 二(三叔丁基膦)钯 、 三乙胺 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.42h， 生成 N4-(piperidin-4-ylmethyl)-N6-(pyridin-3-yl)pyrimidine-4,6-diamine
  参考文献：
  名称：

  Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

  摘要：

  Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.

  DOI：

  10.1021/jm2007326

文献信息

• Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing
  作者：John C. Reader、Thomas P. Matthews、Suki Klair、Kwai-Ming J. Cheung、Jane Scanlon、Nicolas Proisy、Glynn Addison、John Ellard、Nelly Piton、Suzanne Taylor、Michael Cherry、Martin Fisher、Kathy Boxall、Samantha Burns、Michael I. Walton、Isaac M. Westwood、Angela Hayes、Paul Eve、Melanie Valenti、Alexis de Haven Brandon、Gary Box、Rob L. M. van Montfort、David H. Williams、G. Wynne Aherne、Florence I. Raynaud、Suzanne A. Eccles、Michelle D. Garrett、Ian Collins

  DOI：10.1021/jm2007326

  日期：2011.12.22

  Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.