5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-furaldehyde | 675579-69-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-furaldehyde
• 英文别名: 5-(5,5,8,8-Tetramethyl-6,7-dihydronaphthalen-2-yl)furan-2-carbaldehyde；5-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)furan-2-carbaldehyde
• CAS: 675579-69-8
• 化学式: C₁₉H₂₂O₂
• 分子量: 282.382
• InChiKey: ZLEJMMFJQBTYGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-furaldehyde 在 lithium hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 为溶剂， 反应 0.33h， 生成 (E)-3-[5-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-furan-2-yl]-acrylic acid
  参考文献：
  名称：

  Structure-Based Design of Potent Retinoid X Receptor α Agonists

  摘要：

  A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater than 167-fold selective vs RARalpha (K(i) > 1000 nM). This compound profiled out as a full agonist in a cell-based transient transfection assay (EC(50) = 3 nM). The two antipodes were separated via chiral chromatography, and 46b was found to be 40-fold more potent than 46a. Interestingly, cocrystallization of 46a,b with the RXRalpha protein generated a liganded structure whereby the (S)-antipode was found in the binding pocket. Given orally in db/db mice or ZDF rats, 46a,b showed a significant glucose-lowering effect and an increase in liver mass. Triglycerides decreased significantly in db/db mice but increased in the ZDF rats. A dose-dependent decrease of nonesterified free fatty acids was seen in ZDF rats but not in db/db mice. These differences indicate a species specific effect of RXR agonists on lipid metabolism.

  DOI：

  10.1021/jm030565g
• 作为产物：
  描述：

  5-溴-2-呋喃甲醛 、 (5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基)硼酸 在 1,1'-双(二苯基膦)二茂铁 、 碳酸氢钠 、 palladium dichloride 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.5h， 以81%的产率得到5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-furaldehyde
  参考文献：
  名称：

  Structure-Based Design of Potent Retinoid X Receptor α Agonists

  摘要：

  A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater than 167-fold selective vs RARalpha (K(i) > 1000 nM). This compound profiled out as a full agonist in a cell-based transient transfection assay (EC(50) = 3 nM). The two antipodes were separated via chiral chromatography, and 46b was found to be 40-fold more potent than 46a. Interestingly, cocrystallization of 46a,b with the RXRalpha protein generated a liganded structure whereby the (S)-antipode was found in the binding pocket. Given orally in db/db mice or ZDF rats, 46a,b showed a significant glucose-lowering effect and an increase in liver mass. Triglycerides decreased significantly in db/db mice but increased in the ZDF rats. A dose-dependent decrease of nonesterified free fatty acids was seen in ZDF rats but not in db/db mice. These differences indicate a species specific effect of RXR agonists on lipid metabolism.

  DOI：

  10.1021/jm030565g

文献信息

• Structure-Based Design of Potent Retinoid X Receptor α Agonists
  作者：Curt D. Haffner、James M. Lenhard、Aaron B. Miller、Darryl L. McDougald、Kate Dwornik、Olivia R. Ittoop、Robert T. Gampe,、H. Eric Xu、Steve Blanchard、Valerie G. Montana、Tom G. Consler、Randy K. Bledsoe、Andrea Ayscue、Dallas Croom

  DOI：10.1021/jm030565g

  日期：2004.4.1

  A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater than 167-fold selective vs RARalpha (K(i) > 1000 nM). This compound profiled out as a full agonist in a cell-based transient transfection assay (EC(50) = 3 nM). The two antipodes were separated via chiral chromatography, and 46b was found to be 40-fold more potent than 46a. Interestingly, cocrystallization of 46a,b with the RXRalpha protein generated a liganded structure whereby the (S)-antipode was found in the binding pocket. Given orally in db/db mice or ZDF rats, 46a,b showed a significant glucose-lowering effect and an increase in liver mass. Triglycerides decreased significantly in db/db mice but increased in the ZDF rats. A dose-dependent decrease of nonesterified free fatty acids was seen in ZDF rats but not in db/db mice. These differences indicate a species specific effect of RXR agonists on lipid metabolism.