ethyl 6-chloro-4-{[(1S,2R)-2-methylcyclohexyl]amino}nicotinate | 1227486-47-6

• 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: ethyl 6-chloro-4-{[(1S,2R)-2-methylcyclohexyl]amino}nicotinate
• 英文别名: ethyl 6-chloro-4-[[(1S,2R)-2-methylcyclohexyl]amino]pyridine-3-carboxylate
• CAS: 1227486-47-6
• 化学式: C₁₅H₂₁ClN₂O₂
• 分子量: 296.797
• InChiKey: KZNROQILBUVKSH-PWSUYJOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 6-chloro-4-{[(1S,2R)-2-methylcyclohexyl]amino}nicotinate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2′-二环己基膦-2,4,6-三甲氧基联苯 、 N,N'-羰基二咪唑 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 4.5h， 生成 6-anilino-4-{[(1S,2R)-2-methylcyclohexyl]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
• 作为产物：
  描述：

  4,6-二氯烟酸乙酯 、 (1S,2R)-2-甲基环己胺盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 反应 4.0h， 以98%的产率得到ethyl 6-chloro-4-{[(1S,2R)-2-methylcyclohexyl]amino}nicotinate
  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

• 4,6-DIAMINONICOTINAMIDE COMPOUND
  申请人：Shirakami Shohei

  公开号：US20110230467A1

  公开（公告）日：2011-09-22

  [Problem] The present invention provides a 4,6-diaminonicotinamide compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for treating diseases caused by undesirable and/or abnormal cytokine signal transduction. [Means for Solution] The present inventors have extensively studied compounds having a JAK3 inhibitory action, and as a result, they have found that a 4,6-diaminonicotinamide compound which is the compound of the present invention has an excellent JAK3 inhibitory action and is useful as an agent for preventing or treating diseases caused by undesirable and/or abnormal cytokine signal transduction, thereby completing the present invention.

  [问题] 本发明提供了一种4,6-二氨基烟酰胺化合物，该化合物可用作制药组合物的活性成分，特别是用于治疗由不良和/或异常的细胞因子信号传导引起的疾病的制药组合物。 [解决方法] 本发明人广泛研究了具有JAK3抑制作用的化合物，结果发现本发明的4,6-二氨基烟酰胺化合物具有出色的JAK3抑制作用，并且可用作预防或治疗由不良和/或异常的细胞因子信号传导引起的疾病的药剂，从而完成了本发明。
• 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.