4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylmethylamino)benzoic acid ethyl ester | 133023-47-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylmethylamino)benzoic acid ethyl ester
• 英文别名: Ethyl 4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)methylamino]benzoate
• CAS: 133023-47-9
• 化学式: C₂₄H₃₁NO₂
• 分子量: 365.516
• InChiKey: VGFRPIWWQKLAFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylmethylamino)benzoic acid ethyl ester 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以90%的产率得到4-[(5,5,8,8-Tetramethyl-6,7-dihydronaphthalen-2-yl)methylamino]benzoic acid
  参考文献：
  名称：

  Heterocycle-Containing Retinoids. Discovery of a Novel Isoxazole Arotinoid Possessing Potent Apoptotic Activity in Multidrug and Drug-Induced Apoptosis-Resistant Cells

  摘要：

  In a search for retinoic acid (RA) receptor ligands endowed with potent apoptotic activity, a series of novel arotinoids were prepared. Because the stereochemistry of the CS-alkenyl portion of natural 9-cis-RA and the olefinic moiety of the previously synthesized isoxazole retinoid 4 seems to have particular importance for their apoptotic activity, novel retinoid analogues with a restricted or, vice versa, a larger flexibility in this region were designed and prepared. The new compounds were evaluated in vitro for their ability to activate natural retinoid receptors and for their differentiation-inducing activity. Cytotoxic and apoptotic activities were, in addition, evaluated. In general, these analogues showed low cytotoxicity, with the restricted structures being slightly more active than the more flexible ones. As an exception, however, the isoxazole retinoid 15b proved to be particularly able to induce apoptosis at concentrations <5 muM, showing a higher activity than the classical retinoids such as all-trans-RA, 13-cis-RA, and 9-cis-RA and the previously described synthetic retinoid 4. 15b also exhibited a good affinity for the retinoid receptors. Interestingly, another important property of 15b was its ability to induce apoptosis in the HL60R multidrug-resistant (MDR) cell line, at the same concentration as is effective in HL60. Therefore, 15b represents a new retinoid possessing high apoptotic activity in an MDR cell line. The ability of 15b to act on K562 and HL60R cells suggests that this compound may have important implications in the treatment of different leukemias, and its structure could offer an interesting model for the design of new compounds endowed with apoptotic activity on MDR- and retinoid-resistant malignancies.

  DOI：

  10.1021/jm0010320
• 作为产物：
  描述：

  5,5,8,8-四甲基-5,6,7,8-四氢-2-萘甲醛 、 苯佐卡因 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以60%的产率得到4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylmethylamino)benzoic acid ethyl ester
  参考文献：
  名称：

  Heterocycle-Containing Retinoids. Discovery of a Novel Isoxazole Arotinoid Possessing Potent Apoptotic Activity in Multidrug and Drug-Induced Apoptosis-Resistant Cells

  摘要：

  In a search for retinoic acid (RA) receptor ligands endowed with potent apoptotic activity, a series of novel arotinoids were prepared. Because the stereochemistry of the CS-alkenyl portion of natural 9-cis-RA and the olefinic moiety of the previously synthesized isoxazole retinoid 4 seems to have particular importance for their apoptotic activity, novel retinoid analogues with a restricted or, vice versa, a larger flexibility in this region were designed and prepared. The new compounds were evaluated in vitro for their ability to activate natural retinoid receptors and for their differentiation-inducing activity. Cytotoxic and apoptotic activities were, in addition, evaluated. In general, these analogues showed low cytotoxicity, with the restricted structures being slightly more active than the more flexible ones. As an exception, however, the isoxazole retinoid 15b proved to be particularly able to induce apoptosis at concentrations <5 muM, showing a higher activity than the classical retinoids such as all-trans-RA, 13-cis-RA, and 9-cis-RA and the previously described synthetic retinoid 4. 15b also exhibited a good affinity for the retinoid receptors. Interestingly, another important property of 15b was its ability to induce apoptosis in the HL60R multidrug-resistant (MDR) cell line, at the same concentration as is effective in HL60. Therefore, 15b represents a new retinoid possessing high apoptotic activity in an MDR cell line. The ability of 15b to act on K562 and HL60R cells suggests that this compound may have important implications in the treatment of different leukemias, and its structure could offer an interesting model for the design of new compounds endowed with apoptotic activity on MDR- and retinoid-resistant malignancies.

  DOI：

  10.1021/jm0010320

文献信息

• Heterocycle-Containing Retinoids. Discovery of a Novel Isoxazole Arotinoid Possessing Potent Apoptotic Activity in Multidrug and Drug-Induced Apoptosis-Resistant Cells
  作者：Daniele Simoni、Marinella Roberti、Francesco Paolo Invidiata、Riccardo Rondanin、Riccardo Baruchello、Cinzia Malagutti、Angelica Mazzali、Marcello Rossi、Stefania Grimaudo、Francesca Capone、Luisa Dusonchet、Maria Meli、Maria Valeria Raimondi、Marilena Landino、Natale D'Alessandro、Manlio Tolomeo、Dhar Arindam、Shennan Lu、Doris M. Benbrook

  DOI：10.1021/jm0010320

  日期：2001.7.1

  In a search for retinoic acid (RA) receptor ligands endowed with potent apoptotic activity, a series of novel arotinoids were prepared. Because the stereochemistry of the CS-alkenyl portion of natural 9-cis-RA and the olefinic moiety of the previously synthesized isoxazole retinoid 4 seems to have particular importance for their apoptotic activity, novel retinoid analogues with a restricted or, vice versa, a larger flexibility in this region were designed and prepared. The new compounds were evaluated in vitro for their ability to activate natural retinoid receptors and for their differentiation-inducing activity. Cytotoxic and apoptotic activities were, in addition, evaluated. In general, these analogues showed low cytotoxicity, with the restricted structures being slightly more active than the more flexible ones. As an exception, however, the isoxazole retinoid 15b proved to be particularly able to induce apoptosis at concentrations <5 muM, showing a higher activity than the classical retinoids such as all-trans-RA, 13-cis-RA, and 9-cis-RA and the previously described synthetic retinoid 4. 15b also exhibited a good affinity for the retinoid receptors. Interestingly, another important property of 15b was its ability to induce apoptosis in the HL60R multidrug-resistant (MDR) cell line, at the same concentration as is effective in HL60. Therefore, 15b represents a new retinoid possessing high apoptotic activity in an MDR cell line. The ability of 15b to act on K562 and HL60R cells suggests that this compound may have important implications in the treatment of different leukemias, and its structure could offer an interesting model for the design of new compounds endowed with apoptotic activity on MDR- and retinoid-resistant malignancies.