4-(cyclopentylamino)-6-{[(1-oxidopyridin-2-yl)methyl]amino}quinoline-3-carbonitrile | 915364-19-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(cyclopentylamino)-6-{[(1-oxidopyridin-2-yl)methyl]amino}quinoline-3-carbonitrile
• 英文别名: 4-(Cyclopentylamino)-6-[(1-oxidopyridin-1-ium-2-yl)methylamino]quinoline-3-carbonitrile
• CAS: 915364-19-1
• 化学式: C₂₁H₂₁N₅O
• 分子量: 359.431
• InChiKey: GDBGNGLTIWYCJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-pyridinecarboxaldehyde N-oxide 、 6-amino-4-cyclopentylaminoquinoline-3-carbonitrile 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 以28%的产率得到4-(cyclopentylamino)-6-{[(1-oxidopyridin-2-yl)methyl]amino}quinoline-3-carbonitrile
  参考文献：
  名称：

  Identification of a novel class of selective Tpl2 kinase inhibitors: 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles

  摘要：

  We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tp12) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These compounds show good in vitro and in vivo activity against Tp12 and improved pharmacokinetic properties. In addition they are highly selective for Tp12 kinase over other kinases, for example, EGFR, MEK, MK2, and p38. Lead compound 4-cycloheptylamino-6-[(pyridin-3-ylmethyl)-amino]-[1,7]naphthyridine-3-carbonit-rile (30) was efficacious in a rat model of LPS-induced TNF-alpha production. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.06.054

文献信息

• Identification of a novel class of selective Tpl2 kinase inhibitors: 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles
  作者：Neelu Kaila、Neal Green、Huan-Qiu Li、Yonghan Hu、Kristin Janz、Lori Krim Gavrin、Jennifer Thomason、Steve Tam、Dennis Powell、John Cuozzo、J. Perry Hall、Jean-Baptiste Telliez、Sang Hsu、Cheryl Nickerson-Nutter、Qin Wang、Lih-Ling Lin

  DOI：10.1016/j.bmc.2007.06.054

  日期：2007.10

  We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tp12) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These compounds show good in vitro and in vivo activity against Tp12 and improved pharmacokinetic properties. In addition they are highly selective for Tp12 kinase over other kinases, for example, EGFR, MEK, MK2, and p38. Lead compound 4-cycloheptylamino-6-[(pyridin-3-ylmethyl)-amino]-[1,7]naphthyridine-3-carbonit-rile (30) was efficacious in a rat model of LPS-induced TNF-alpha production. (C) 2007 Elsevier Ltd. All rights reserved.