4-[1-(3-Butyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoic acid methyl ester | 758690-13-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4-[1-(3-Butyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoic acid methyl ester
• CAS: 758690-13-0
• 化学式: C₂₈H₃₆O₂
• 分子量: 404.593
• InChiKey: XSUNRUZXWJCTNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.23
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-[1-(3-Butyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoic acid methyl ester 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以93%的产率得到4-[1-(3-Butyl-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethenyl]benzoic acid
  参考文献：
  名称：

  Determinants of Retinoid X Receptor Transcriptional Antagonism

  摘要：

  The synthesis and bloactivity of the retinoid X receptor (RXR) antagonist 4-[(3'-n-butyl-5',6', 7',8'-tetrahydro-5',5',8',8'-tetramethyl-2'-naphthalenyl)(cyclopropylidene)methyl]benzoic acid and several heteroatom-substituted analogues are described. Ligand design was based on the scaffold of the X-methyl RXR-selective agonist analogue and reports that 3'-n-propyl and longer n-alkyl groups conferred RXR antagonism. The transcriptional antagonism of the 3'-n-butyl analogue was demonstrated by its blockade of retinoic acid receptor (RAR) beta expression induced by the RXRalpha/peroxisome proliferator-activated receptor (PPAR) gamma heterodimer complexed with an RXRalpha agonist plus the PPARgamma agonist ciglitazone and the inhibition of 9-cis-RA-induced coactivator SRC-1a recruitment to RXRalpha. Receptor-ligand docking studies using full-atom flexible ligand and flexible receptor suggested that binding of the antagonist to the RXRa antagonist conformation was favored because the salt bridge that formed between the retinoid carboxylate and the RXRalpha helix H5 arginine-321 was far stronger than that formed on its binding to the agonist conformation. The antagonist also blocked activation of RAR subtypes alpha and beta by 9-cis-RA but not that of RARgamma.

  DOI：

  10.1021/jm030651g
• 作为产物：
  描述：

  6-溴-1,1,4,4-四甲基-1,2,3,4-四氢化萘 在 正丁基锂 、 三氯化铝 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 4.25h， 生成 4-[1-(3-Butyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoic acid methyl ester
  参考文献：
  名称：

  Determinants of Retinoid X Receptor Transcriptional Antagonism

  摘要：

  The synthesis and bloactivity of the retinoid X receptor (RXR) antagonist 4-[(3'-n-butyl-5',6', 7',8'-tetrahydro-5',5',8',8'-tetramethyl-2'-naphthalenyl)(cyclopropylidene)methyl]benzoic acid and several heteroatom-substituted analogues are described. Ligand design was based on the scaffold of the X-methyl RXR-selective agonist analogue and reports that 3'-n-propyl and longer n-alkyl groups conferred RXR antagonism. The transcriptional antagonism of the 3'-n-butyl analogue was demonstrated by its blockade of retinoic acid receptor (RAR) beta expression induced by the RXRalpha/peroxisome proliferator-activated receptor (PPAR) gamma heterodimer complexed with an RXRalpha agonist plus the PPARgamma agonist ciglitazone and the inhibition of 9-cis-RA-induced coactivator SRC-1a recruitment to RXRalpha. Receptor-ligand docking studies using full-atom flexible ligand and flexible receptor suggested that binding of the antagonist to the RXRa antagonist conformation was favored because the salt bridge that formed between the retinoid carboxylate and the RXRalpha helix H5 arginine-321 was far stronger than that formed on its binding to the agonist conformation. The antagonist also blocked activation of RAR subtypes alpha and beta by 9-cis-RA but not that of RARgamma.

  DOI：

  10.1021/jm030651g