5-hydroxy-2-naphthyl trifluoromethanesulfonate | 1268826-55-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-hydroxy-2-naphthyl trifluoromethanesulfonate
• 英文别名: 5-Hydroxy-2-naphthyl trifluoromethanesulfonate；(5-hydroxynaphthalen-2-yl) trifluoromethanesulfonate
• CAS: 1268826-55-6
• 化学式: C₁₁H₇F₃O₄S
• 分子量: 292.235
• InChiKey: DUGJKDVFMXBZRI-UHFFFAOYSA-N

物化性质

• 沸点：
  405.1±45.0 °C(Predicted)
• 密度：
  1.593±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2-naphthyl trifluoromethanesulfonate 在 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 18-冠醚-6 、 potassium acetate 、 三溴化硼 、 potassium carbonate 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， -78.0~150.0 ℃ 、1.5 MPa 条件下， 反应 4.67h， 生成 5-(5-hydroxy-2-naphthyl)biphenyl-2-ol
  参考文献：
  名称：

  Introduction of an Electron Withdrawing Group on the Hydroxyphenylnaphthol Scaffold Improves the Potency of 17β-Hydroxysteroid Dehydrogenase Type 2 (17β-HSD2) Inhibitors

  摘要：

  Estrogen deficiency in postmenopausal women or elderly men is often associated with the skeletal disease osteoporosis. The supplementation of estradiol (E2) in osteoporotic patients is known to prevent bone fracture but cannot be administered because of adverse effect. As 17 beta-hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) oxidizes E2 to its inactive form estrone (E1) and has been found in osteoblastic cells, it is an attractive target for the treatment of osteoporosis. Twenty-one novel, naphthalene-derived compounds have been synthesized and evaluated for their 17 beta-HSD2 inhibition and their selectivity toward 17 beta-HSD1 and the estrogen receptors (ERs) alpha and beta. Compound 19 turned out to be the most potent and selective inhibitor of 17 beta-HSD2 in cell-free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17 beta-HSD2. It also showed marked inhibition of the E1-formation by the rat and mouse orthologous enzymes and strong inhibition of monkey 17 beta-HSD2. It is thus an appropriate candidate to be further evaluated in a disease-oriented model.

  DOI：

  10.1021/jm2008453
• 作为产物：
  描述：

  6-羟基-1-四氢萘酮 在 吡啶 、 盐酸 、 溴 、 lithium carbonate 、 lithium bromide 作用下， 以 四氯化碳 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 5-hydroxy-2-naphthyl trifluoromethanesulfonate
  参考文献：
  名称：

  17β-HSD2 inhibitors for the treatment of osteoporosis: Identification of a promising scaffold

  摘要：

  17 beta-Hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) catalyses the conversion of active 17 beta-hydroxysteroids into the less active 17-ketosteroids thereby controlling the availability of biologically active estrogens (E2) and androgens (T) in the tissues. The skeletal disease osteoporosis occurs mainly in post-menopausal women and in elderly men when the levels of estrogens and androgens, respectively, decrease. Since 17 beta-HSD2 is present in osteoblasts, inhibition of this enzyme may provide a new and promising approach to prevent the onset of osteoporosis, keeping a certain level in estrogens and androgens in bone cells of ageing people. Hydroxynaphthyl, hydroxyphenyl and hydroxymethylphenyl-substituted moieties were synthesised as mimetics of the steroidal substrate. Compound 8 has been identified as promising scaffold for 17 beta-HSD2 inhibitors displaying high activity and good selectivity toward 17 beta-HSD1, ER alpha and ER beta. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.013

文献信息

• JP2016/88927
  申请人：——

  公开号：——

  公开（公告）日：——
• 17β-HSD2 inhibitors for the treatment of osteoporosis: Identification of a promising scaffold
  作者：Marie Wetzel、Sandrine Marchais-Oberwinkler、Rolf W. Hartmann

  DOI：10.1016/j.bmc.2010.12.013

  日期：2011.1

  17 beta-Hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) catalyses the conversion of active 17 beta-hydroxysteroids into the less active 17-ketosteroids thereby controlling the availability of biologically active estrogens (E2) and androgens (T) in the tissues. The skeletal disease osteoporosis occurs mainly in post-menopausal women and in elderly men when the levels of estrogens and androgens, respectively, decrease. Since 17 beta-HSD2 is present in osteoblasts, inhibition of this enzyme may provide a new and promising approach to prevent the onset of osteoporosis, keeping a certain level in estrogens and androgens in bone cells of ageing people. Hydroxynaphthyl, hydroxyphenyl and hydroxymethylphenyl-substituted moieties were synthesised as mimetics of the steroidal substrate. Compound 8 has been identified as promising scaffold for 17 beta-HSD2 inhibitors displaying high activity and good selectivity toward 17 beta-HSD1, ER alpha and ER beta. (C) 2010 Elsevier Ltd. All rights reserved.
• Introduction of an Electron Withdrawing Group on the Hydroxyphenylnaphthol Scaffold Improves the Potency of 17β-Hydroxysteroid Dehydrogenase Type 2 (17β-HSD2) Inhibitors
  作者：Marie Wetzel、Sandrine Marchais-Oberwinkler、Enrico Perspicace、Gabriele Möller、Jerzy Adamski、Rolf W. Hartmann

  DOI：10.1021/jm2008453

  日期：2011.11.10

  Estrogen deficiency in postmenopausal women or elderly men is often associated with the skeletal disease osteoporosis. The supplementation of estradiol (E2) in osteoporotic patients is known to prevent bone fracture but cannot be administered because of adverse effect. As 17 beta-hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) oxidizes E2 to its inactive form estrone (E1) and has been found in osteoblastic cells, it is an attractive target for the treatment of osteoporosis. Twenty-one novel, naphthalene-derived compounds have been synthesized and evaluated for their 17 beta-HSD2 inhibition and their selectivity toward 17 beta-HSD1 and the estrogen receptors (ERs) alpha and beta. Compound 19 turned out to be the most potent and selective inhibitor of 17 beta-HSD2 in cell-free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17 beta-HSD2. It also showed marked inhibition of the E1-formation by the rat and mouse orthologous enzymes and strong inhibition of monkey 17 beta-HSD2. It is thus an appropriate candidate to be further evaluated in a disease-oriented model.