ethyl 5-(5,6,7,8-tetrahydro-3,5,5,7,8,8-hexamethyl-2-naphthalenyl)isoxazole-3-carboxylate | 252769-73-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: ethyl 5-(5,6,7,8-tetrahydro-3,5,5,7,8,8-hexamethyl-2-naphthalenyl)isoxazole-3-carboxylate
• 英文别名: Ethyl 5-(3,5,5,7,8,8-hexamethyl-6,7-dihydronaphthalen-2-yl)-1,2-oxazole-3-carboxylate
• CAS: 252769-73-6
• 化学式: C₂₂H₂₉NO₃
• 分子量: 355.477
• InChiKey: HASHCJUTOJFFBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 5-(5,6,7,8-tetrahydro-3,5,5,7,8,8-hexamethyl-2-naphthalenyl)isoxazole-3-carboxylate 在 lithium hydroxide 、 水 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以95%的产率得到5-(3,5,5,7,8,8-Hexamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-isoxazole-3-carboxylic acid
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Heteroretinoids:  Induction of Apoptosis in the HL-60 Cell Line by a Novel Isoxazole-Containing Heteroretinoid

  摘要：

  In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were nest active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, compound 13b, which has the trans stereochemistry at the double bond, was found not to be active in the apoptotic assay, but it was endowed with appreciable differentiating activity. Therefore, it seems that the different stereochemistry of the double bond may be associated with a different biological activity: potent apoptotic activity for the cis-isomer but differentiating activity for the traits structure. This biological behavior was found, at least in part, for the 9-cis- and 13-cis-retinoic acids with respect to the all-trans-retinoic acid. Thus, structure 14b could offer an interesting model for the design of new compounds endowed with apoptotic activity.

  DOI：

  10.1021/jm991059n
• 作为产物：
  描述：

  7-acetyl-1,1,2,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene 在 盐酸羟胺 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 ethyl 5-(5,6,7,8-tetrahydro-3,5,5,7,8,8-hexamethyl-2-naphthalenyl)isoxazole-3-carboxylate
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Heteroretinoids:  Induction of Apoptosis in the HL-60 Cell Line by a Novel Isoxazole-Containing Heteroretinoid

  摘要：

  In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were nest active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, compound 13b, which has the trans stereochemistry at the double bond, was found not to be active in the apoptotic assay, but it was endowed with appreciable differentiating activity. Therefore, it seems that the different stereochemistry of the double bond may be associated with a different biological activity: potent apoptotic activity for the cis-isomer but differentiating activity for the traits structure. This biological behavior was found, at least in part, for the 9-cis- and 13-cis-retinoic acids with respect to the all-trans-retinoic acid. Thus, structure 14b could offer an interesting model for the design of new compounds endowed with apoptotic activity.

  DOI：

  10.1021/jm991059n

文献信息

• Structure−Activity Relationship Studies of Novel Heteroretinoids:  Induction of Apoptosis in the HL-60 Cell Line by a Novel Isoxazole-Containing Heteroretinoid
  作者：Daniele Simoni、Francesco Paolo Invidiata、Riccardo Rondanin、Stefania Grimaudo、Giuliana Cannizzo、Eleonora Barbusca、Ferdinando Porretto、Nicola D'Alessandro、Manlio Tolomeo

  DOI：10.1021/jm991059n

  日期：1999.12.2

  In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were nest active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, compound 13b, which has the trans stereochemistry at the double bond, was found not to be active in the apoptotic assay, but it was endowed with appreciable differentiating activity. Therefore, it seems that the different stereochemistry of the double bond may be associated with a different biological activity: potent apoptotic activity for the cis-isomer but differentiating activity for the traits structure. This biological behavior was found, at least in part, for the 9-cis- and 13-cis-retinoic acids with respect to the all-trans-retinoic acid. Thus, structure 14b could offer an interesting model for the design of new compounds endowed with apoptotic activity.