methyl 6-(ethyl(3-isopropoxy-4-isopropylphenyl)amino)nicotinate | 1055233-31-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: methyl 6-(ethyl(3-isopropoxy-4-isopropylphenyl)amino)nicotinate
• CAS: 1055233-31-2
• 化学式: C₂₁H₂₈N₂O₃
• 分子量: 356.465
• InChiKey: MUWUKENVTZWAHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.94
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  51.66
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 6-(ethyl(3-isopropoxy-4-isopropylphenyl)amino)nicotinate 在 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.67h， 生成 NEt-3IP
  参考文献：
  名称：

  REXINOID COMPOUND HAVING ALKOXY GROUP

  摘要：

  公开号：

  EP2116523B1
• 作为产物：
  描述：

  2-isopropoxy-1-isopropyl-4-nitrobenzene 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 、 溶剂黄146 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.58h， 生成 methyl 6-(ethyl(3-isopropoxy-4-isopropylphenyl)amino)nicotinate
  参考文献：
  名称：

  REXINOID COMPOUND HAVING ALKOXY GROUP

  摘要：

  公开号：

  EP2116523B1

文献信息

• Positron Emission Tomography to Elucidate Pharmacokinetic Differences of Regioisomeric Retinoid X Receptor Agonists
  作者：Toshiki Kobayashi、Yuki Furusawa、Shoya Yamada、Masaru Akehi、Fumiaki Takenaka、Takanori Sasaki、Akiya Akahoshi、Takahisa Hanada、Eiji Matsuura、Hiroyuki Hirano、Akihiro Tai、Hiroki Kakuta

  DOI：10.1021/ml500511m

  日期：2015.3.12

  RXR partial agonist NEt-41B (2a, 6-[ethyl-(4-isobutoxy-3-isopropylphenyl)amino]pyridine-3-carboxylic acid: EC50 = 169 nM, E-max = 55%) showed a blood concentration higher than its Emax after single oral administration at 30 mg/kg to mice, and repeated oral administration at 10 mg/kg/day to KK-A(y) mice afforded antitype 2 diabetes activity without the side effects caused by RXR full agonists. However, RXR full agonist NEt-3IB (la), in which the isobutoxy and isopropyl groups of 2a are interchanged, gave a much lower blood concentration than 2a. Here we used positron emission tomography (PET) with tracers [C-11] la, [C-11]2a and fluorinated derivatives [F-18] lb, [F-18]2b, which have longer half-lives, to examine the reason why la and 2a exhibited significantly different blood concentrations. As a result, the reason for the high blood concentration of 2a after oral administration was found to be linked to higher intestinal absorbability together with lower biliary excretion, compared with la.
• Modification at the Lipophilic Domain of RXR Agonists Differentially Influences Activation of RXR Heterodimers
  作者：Fuminori Ohsawa、Ken-ichi Morishita、Shoya Yamada、Makoto Makishima、Hiroki Kakuta

  DOI：10.1021/ml100184k

  日期：2010.12.9

  RXR permissive heterodimers are reported to be activated differently depending upon the chemical structure of RXR agonists, but the relationship of agonist structure to differential heterodimer activation has not been explored in detail. In this study, we performed systematic conversion of the alkoxy side chain of 5a (6-[ethyl-(3-isopropoxy-4-isopropylphenyl)amino]nicotinic acid, NEt-3IP) and evaluated the RXR-, PPAR/RXR-, and LXR/RXR-agonist activities of the products. The cyclopropylmethoxy analogue (5c) showed similar RXR- and LXR/RXR-agonistic activities to the benzyloxy analogue (51) and n-propoxy analogue (5k) but exhibited more potent PPAR/RXR-agonistic activity than 51 or 5k. Differential modulation of RXR heterodimer-activating ability by conversion of the alkoxy group located in the lipophilic domain of the RXR-agonist common structure is expected be a useful approach in the design of new RXR agonists for the treatment of hyperlipidemia or type 2 diabetes.