ethyl (2E)-3-[4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-4,5,6,7-tetrahydro-1-benzofuran-2-yl]-2-propenoate | 503620-68-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (2E)-3-[4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-4,5,6,7-tetrahydro-1-benzofuran-2-yl]-2-propenoate
• 英文别名: ethyl (E)-3-[4-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)-4,5,6,7-tetrahydro-1-benzofuran-2-yl]prop-2-enoate
• CAS: 503620-68-6
• 化学式: C₂₈H₃₆O₃
• 分子量: 420.592
• InChiKey: ZQRDYWJVAFGGRD-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (2E)-3-[4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-4,5,6,7-tetrahydro-1-benzofuran-2-yl]-2-propenoate 在 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 以80%的产率得到(E)-3-[4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-4,5,6,7-tetrahydro-benzofuran-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：

  6,7-二氢-4(5H)-苯并呋喃酮 在 sodium tetrahydroborate 、 正丁基锂 、 三氟化硼乙醚 、 sodium hydride 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 为溶剂， 反应 2.17h， 生成 ethyl (2E)-3-[4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-4,5,6,7-tetrahydro-1-benzofuran-2-yl]-2-propenoate
  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