NEt-4IP | 1041186-82-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: NEt-4IP
• 英文别名: 6-(N-ethyl-3-propan-2-yl-4-propan-2-yloxyanilino)pyridine-3-carboxylic acid
• CAS: 1041186-82-6
• 化学式: C₂₀H₂₆N₂O₃
• 分子量: 342.438
• InChiKey: RRLRNRBXEKMPAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  62.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-异丙基-4-硝基苯酚 在 甲烷磺酸 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 31.46h， 生成 NEt-4IP
  参考文献：
  名称：

  RXR Partial Agonist Produced by Side Chain Repositioning of Alkoxy RXR Full Agonist Retains Antitype 2 Diabetes Activity without the Adverse Effects

  摘要：

  We previously reported RXR partial agonist CBt-PMN (1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid: 5, EC50 = 143 nM, E-max = 75%), which showed a potent glucose-lowering effect without causing serious adverse effects. However, it remains important to elucidate the structural requirements for RXR efficacy and the glucose-lowering effect because RXR-permissive heterodimers such as PPAR/RXR or LXR/RXR are reported to be activated differently depending upon the chemical structure of RXR agonists. In this work, we show that an RXR partial agonist, NEt-4IB (6-[ethyl-(4-isobutoxy-3-isopropylphenyl)amino]pyridine-3-carboxylic acid: 8b, EC50 = 169 nM, E-max = 55%), can be obtained simply by repositioning the side chains (interchanging the isobutoxy and isopropoxy groups) at the hydrophobic moiety of the RXR full agonist NEt-3IB (6-[ethyl-(3-isobutoxy-4-isopropylphenyl)amino]pyridine-3-carboxylic acid: 7b, EC50 = 19 nM). NEt-4IB (8b) showed antitype 2 diabetes activity without the above side effects upon repeated oral administration to mice at 10 mg/kg/day, similarly to 5.

  DOI：

  10.1021/jm501863r

文献信息

• RXR Partial Agonist Produced by Side Chain Repositioning of Alkoxy RXR Full Agonist Retains Antitype 2 Diabetes Activity without the Adverse Effects
  作者：Kohei Kawata、Ken-ichi Morishita、Mariko Nakayama、Shoya Yamada、Toshiki Kobayashi、Yuki Furusawa、Sakae Arimoto-Kobayashi、Toshitaka Oohashi、Makoto Makishima、Hirotaka Naitou、Erika Ishitsubo、Hiroaki Tokiwa、Akihiro Tai、Hiroki Kakuta

  DOI：10.1021/jm501863r

  日期：2015.1.22

  We previously reported RXR partial agonist CBt-PMN (1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid: 5, EC50 = 143 nM, E-max = 75%), which showed a potent glucose-lowering effect without causing serious adverse effects. However, it remains important to elucidate the structural requirements for RXR efficacy and the glucose-lowering effect because RXR-permissive heterodimers such as PPAR/RXR or LXR/RXR are reported to be activated differently depending upon the chemical structure of RXR agonists. In this work, we show that an RXR partial agonist, NEt-4IB (6-[ethyl-(4-isobutoxy-3-isopropylphenyl)amino]pyridine-3-carboxylic acid: 8b, EC50 = 169 nM, E-max = 55%), can be obtained simply by repositioning the side chains (interchanging the isobutoxy and isopropoxy groups) at the hydrophobic moiety of the RXR full agonist NEt-3IB (6-[ethyl-(3-isobutoxy-4-isopropylphenyl)amino]pyridine-3-carboxylic acid: 7b, EC50 = 19 nM). NEt-4IB (8b) showed antitype 2 diabetes activity without the above side effects upon repeated oral administration to mice at 10 mg/kg/day, similarly to 5.