2-[N-ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)]-5-(2H-tetrazol-5-yl)pyridinamine | 1246265-74-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-[N-ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)]-5-(2H-tetrazol-5-yl)pyridinamine
• 英文别名: N-ethyl-N-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-5-(2H-tetrazol-5-yl)pyridin-2-amine
• CAS: 1246265-74-6
• 化学式: C₂₂H₂₈N₆
• 分子量: 376.505
• InChiKey: LAVVEKRPDLBLLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  70.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-[N-ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]-3-pyridinecarbonitrile 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以43%的产率得到2-[N-ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)]-5-(2H-tetrazol-5-yl)pyridinamine
  参考文献：
  名称：

  Modification at the acidic domain of RXR agonists has little effect on permissive RXR-heterodimer activation

  摘要：

  Retinoid X receptors (RXRs) function as homo-or heterodimers with other nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs), which are targets for treatment of hyperlipidemia and type 2 diabetes, or liver X receptors (LXRs), which are involved in glucose/lipid metabolism. PPAR/RXR or LXR/RXR are known as permissive RXR-heterodimers because they are activated by RXR agonists alone. Interestingly, the pattern of RXR-heterodimer activation is different depending on the RXR agonist structure, but the structure-activity relationship has not been reported. Here we show that modification or replacement of the carboxyl group in the acidic domain of RXR agonists has little or no effect on permissive RXR-heterodimer activation. Phosphonic acid (9), tetrazole (10), and hydroxamic acid (12) analogues were synthesized from the common bromo intermediate 7. Except for 9, these compounds showed RXR full-agonistic activities in the concentration range of 1-10 mu M. The order of agonistic activity toward both PPAR gamma/RXR alpha and LXR alpha/RXR alpha was the same as it was for RXR, that is, 11 > 10 > 12. These results should be useful for the development of RXR agonists with improved bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.012

文献信息

• Modification at the acidic domain of RXR agonists has little effect on permissive RXR-heterodimer activation
  作者：Shuji Fujii、Fuminori Ohsawa、Shoya Yamada、Ryosuke Shinozaki、Ryosuke Fukai、Makoto Makishima、Shuichi Enomoto、Akihiro Tai、Hiroki Kakuta

  DOI：10.1016/j.bmcl.2010.07.012

  日期：2010.9

  Retinoid X receptors (RXRs) function as homo-or heterodimers with other nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs), which are targets for treatment of hyperlipidemia and type 2 diabetes, or liver X receptors (LXRs), which are involved in glucose/lipid metabolism. PPAR/RXR or LXR/RXR are known as permissive RXR-heterodimers because they are activated by RXR agonists alone. Interestingly, the pattern of RXR-heterodimer activation is different depending on the RXR agonist structure, but the structure-activity relationship has not been reported. Here we show that modification or replacement of the carboxyl group in the acidic domain of RXR agonists has little or no effect on permissive RXR-heterodimer activation. Phosphonic acid (9), tetrazole (10), and hydroxamic acid (12) analogues were synthesized from the common bromo intermediate 7. Except for 9, these compounds showed RXR full-agonistic activities in the concentration range of 1-10 mu M. The order of agonistic activity toward both PPAR gamma/RXR alpha and LXR alpha/RXR alpha was the same as it was for RXR, that is, 11 > 10 > 12. These results should be useful for the development of RXR agonists with improved bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.