4-(benzylamino)-6-[methyl(phenyl)amino]nicotinamide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(benzylamino)-6-[methyl(phenyl)amino]nicotinamide
• 英文别名: 4-(benzylamino)-6-(N-methylanilino)pyridine-3-carboxamide
• 化学式: C₂₀H₂₀N₄O
• 分子量: 332.405
• InChiKey: ALOLMLZROWSAKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(benzylamino)-6-chloronicotinic acid 在 四乙基氯化铵 、 N,N'-羰基二咪唑 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 4-(benzylamino)-6-[methyl(phenyl)amino]nicotinamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3

  摘要：

  In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.08.007

文献信息

• Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3
  作者：Yutaka Nakajima、Naohiro Aoyama、Fumie Takahashi、Hiroshi Sasaki、Keiko Hatanaka、Ayako Moritomo、Masamichi Inami、Misato Ito、Koji Nakamura、Fumihiro Nakamori、Takayuki Inoue、Shohei Shirakami

  DOI：10.1016/j.bmc.2016.08.007

  日期：2016.10

  In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. (C) 2016 Elsevier Ltd. All rights reserved.