ethyl 3-(4-methylamino-2-methanesulfanyl-pyrimidin-5-yl)acrylate | 211244-86-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ethyl 3-(4-methylamino-2-methanesulfanyl-pyrimidin-5-yl)acrylate
• 英文别名: Ethyl 3-[4-(methylamino)-2-methylsulfanylpyrimidin-5-yl]prop-2-enoate
• CAS: 211244-86-9
• 化学式: C₁₁H₁₅N₃O₂S
• 分子量: 253.325
• InChiKey: ANEUYCSYAQMCPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-methylamino-2-methanesulfanyl-pyrimidin-5-yl)acrylate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 反应 12.0h， 生成 8-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors

  摘要：

  A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 mu M), had high potency in functional cell based assays, and had high stability in human liver microsome (t(1/2) = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 angstrom. These structures elucidated the binding mode (Type-1 binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.

  DOI：

  10.1021/ml500474d
• 作为产物：
  描述：

  4-甲胺基-2-甲硫基-5-嘧啶甲酸乙酯 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 15.0h， 生成 ethyl 3-(4-methylamino-2-methanesulfanyl-pyrimidin-5-yl)acrylate
  参考文献：
  名称：

  Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors

  摘要：

  A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 mu M), had high potency in functional cell based assays, and had high stability in human liver microsome (t(1/2) = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 angstrom. These structures elucidated the binding mode (Type-1 binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.

  DOI：

  10.1021/ml500474d