8-Ethyl-7-isopropyl-4-methyl-1-oxa-spiro[5.5]undeca-3,7-dien-2-one | 164266-49-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-Ethyl-7-isopropyl-4-methyl-1-oxa-spiro[5.5]undeca-3,7-dien-2-one
• 英文别名: 10-Ethyl-4-methyl-11-propan-2-yl-1-oxaspiro[5.5]undeca-3,10-dien-2-one
• CAS: 164266-49-3
• 化学式: C₁₆H₂₄O₂
• 分子量: 248.365
• InChiKey: XCSSELGLBWQLOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-Ethyl-7-isopropyl-4-methyl-1-oxa-spiro[5.5]undeca-3,7-dien-2-one 在 lithium aluminium tetrahydride 、 水 作用下， 以 乙醚 为溶剂， 反应 0.25h， 生成 (Z)-4-(3-Ethyl-2-isopropyl-cyclohex-2-enyl)-3-methyl-but-2-en-1-ol
  参考文献：
  名称：

  Conformationally Defined 6-s-trans-Retinoic Acid Analogs. 2. Selective Agonists for Nuclear Receptor Binding and Transcriptional Activity

  摘要：

  We recently demonstrated in animal models that a new conformationally defined RA isomer (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) was as effective as RA in the prevention of skin papillomas but was less toxic. In order to provide more details concerning this improved action, we report here the preparation of a homologous conformationally defined 6-s-trans-retinoid (1) and investigate its ability to interact with proteins and to activate gene expression. Four configurational isomers of 1 were evaluated in binding assays for cellular retinoic acid binding protein, CRABP (isolated from chick skin); CRABP-I and CRABP-II (cloned from mouse); nuclear retinoic acid receptors (RARs); and nuclear retinoid X receptors (RXRs). In each assay the all-E-isomer of this retinoid had an activity that was comparable to that of (all-E)-RA. However, the 9Z-isomer was at least 200-fold less active than (all-E)-RA in binding to different RARs, while it was only 6-20 times less active than (9Z)-RA in binding to different RXRs. In an in vivo transient transfection assay, the all-E-isomer activated a reporter gene containing a retinoic acid response element (RARE) with efficiency similar to (all-E)-RA when expression vectors for either RAR alpha, RAR beta, RAR gamma alone or RAR alpha together with RXR alpha were cotransfected. In contrast, the 9Z-isomer was much less active than (9Z)-RA. in the same assay systems. However, (9Z)-1 efficiently enhanced the DNA binding and transactivational activity of RXR alpha homodimers. Taken together, these studies demonstrate that the all-E- and 9Z-isomers of this retinoid are selective and potent agonists of RAR and RXR binding and activation.

  DOI：

  10.1021/jm00013a006
• 作为产物：
  描述：

  (E)-乙基4-溴-3-甲基-2-丁烯酸酯 、 2-isopropyl-3-ethyl-2-cyclohexenone 在 锌 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 8-Ethyl-7-isopropyl-4-methyl-1-oxa-spiro[5.5]undeca-3,7-dien-2-one
  参考文献：
  名称：

  Conformationally Defined 6-s-trans-Retinoic Acid Analogs. 2. Selective Agonists for Nuclear Receptor Binding and Transcriptional Activity

  摘要：

  We recently demonstrated in animal models that a new conformationally defined RA isomer (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) was as effective as RA in the prevention of skin papillomas but was less toxic. In order to provide more details concerning this improved action, we report here the preparation of a homologous conformationally defined 6-s-trans-retinoid (1) and investigate its ability to interact with proteins and to activate gene expression. Four configurational isomers of 1 were evaluated in binding assays for cellular retinoic acid binding protein, CRABP (isolated from chick skin); CRABP-I and CRABP-II (cloned from mouse); nuclear retinoic acid receptors (RARs); and nuclear retinoid X receptors (RXRs). In each assay the all-E-isomer of this retinoid had an activity that was comparable to that of (all-E)-RA. However, the 9Z-isomer was at least 200-fold less active than (all-E)-RA in binding to different RARs, while it was only 6-20 times less active than (9Z)-RA in binding to different RXRs. In an in vivo transient transfection assay, the all-E-isomer activated a reporter gene containing a retinoic acid response element (RARE) with efficiency similar to (all-E)-RA when expression vectors for either RAR alpha, RAR beta, RAR gamma alone or RAR alpha together with RXR alpha were cotransfected. In contrast, the 9Z-isomer was much less active than (9Z)-RA. in the same assay systems. However, (9Z)-1 efficiently enhanced the DNA binding and transactivational activity of RXR alpha homodimers. Taken together, these studies demonstrate that the all-E- and 9Z-isomers of this retinoid are selective and potent agonists of RAR and RXR binding and activation.

  DOI：

  10.1021/jm00013a006