4-(t-butyldimethylsilyloxy)-α-thioacetyl-toluene | 245076-33-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(t-butyldimethylsilyloxy)-α-thioacetyl-toluene
• 英文别名: ethanethioic acid, S-[4-(tert-butyldimethylsilyloxy)benzyl] ester；S-[[4-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl] ethanethioate
• CAS: 245076-33-9
• 化学式: C₁₅H₂₄O₂SSi
• 分子量: 296.506
• InChiKey: BBBKZKMHELPZRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.85
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(t-butyldimethylsilyloxy)-α-thioacetyl-toluene 在 lithium aluminium tetrahydride 、 sodium 作用下， 以 四氢呋喃 为溶剂， 反应 3.75h， 生成 3-oxo-17α-pregna-4-ene-7α-[(4-t-butyldimethylsilyloxy)benzylthia]-21,17-carbolactone
  参考文献：
  名称：

  Spironolactone-related inhibitors of type II 17β-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities

  摘要：

  The family of 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) catalyzes the formation and inactivation of testosterone (T), dihydrotestosterone (DHT), and estradiol (E-2), thus playing a crucial role in the regulation of active steroid hormones in target tissues. Among the five known 17 beta-HSD enzymes, type II catalyzes the oxidation of E-2 into estrone (El), T into androstenedione, DHT into androstanedione, and 20 alpha-dihydroprogesterone into progesterone. Specific inhibitors are thus an interesting means to study the regulation and to probe the structure of type II 17 beta-HSD. In this context, we have efficiently synthesized a series of 7 alpha-thioalkyl and 7 alpha-thioaryl derivatives of spironolactone that inhibit type II 17 beta-HSD. These new C19-steroidal inhibitors possess two important pharmacophores, namely 17-spiro-gamma-lactone and a bulky side-chain at the 7 alpha-position. It was found that a para-substituted benzylthio group at the 7 alpha-position enhances the inhibitory potency of spironolactone derivatives on type II 17 beta-HSD. In fact, the compound with a para-hydroxy-benzylthio group showed an IC50 value of 0.5 mu M against type II 17 beta-HSD, whereas the compound with a para-[2-(1-piperidinyl)-ethoxy]-benzylthio group inhibited this enzyme with an IC50 value of 0.7 mu M. The latter inhibitor is more selective than the former because it did not show any inhibitory potency against P450 aromatase as well as any affinity towards four steroid receptors (AR, PR, GR, ER). As a result, this inhibitor did not show any proliferative effect on androgen-sensitive Shionogi cells and estrogen-sensitive ZR-75-1 cells. These findings contribute to a better knowledge of the structure of type II 17 beta-HSD and offer an interesting tool to study the regulation of this enzyme in several biological systems. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00260-0
• 作为产物：
  描述：

  4-[(叔-丁基二甲基甲硅烷)氧代]苯甲醛 在 sodium tetrahydroborate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.75h， 生成 4-(t-butyldimethylsilyloxy)-α-thioacetyl-toluene
  参考文献：
  名称：

  Spironolactone-related inhibitors of type II 17β-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities

  摘要：

  The family of 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) catalyzes the formation and inactivation of testosterone (T), dihydrotestosterone (DHT), and estradiol (E-2), thus playing a crucial role in the regulation of active steroid hormones in target tissues. Among the five known 17 beta-HSD enzymes, type II catalyzes the oxidation of E-2 into estrone (El), T into androstenedione, DHT into androstanedione, and 20 alpha-dihydroprogesterone into progesterone. Specific inhibitors are thus an interesting means to study the regulation and to probe the structure of type II 17 beta-HSD. In this context, we have efficiently synthesized a series of 7 alpha-thioalkyl and 7 alpha-thioaryl derivatives of spironolactone that inhibit type II 17 beta-HSD. These new C19-steroidal inhibitors possess two important pharmacophores, namely 17-spiro-gamma-lactone and a bulky side-chain at the 7 alpha-position. It was found that a para-substituted benzylthio group at the 7 alpha-position enhances the inhibitory potency of spironolactone derivatives on type II 17 beta-HSD. In fact, the compound with a para-hydroxy-benzylthio group showed an IC50 value of 0.5 mu M against type II 17 beta-HSD, whereas the compound with a para-[2-(1-piperidinyl)-ethoxy]-benzylthio group inhibited this enzyme with an IC50 value of 0.7 mu M. The latter inhibitor is more selective than the former because it did not show any inhibitory potency against P450 aromatase as well as any affinity towards four steroid receptors (AR, PR, GR, ER). As a result, this inhibitor did not show any proliferative effect on androgen-sensitive Shionogi cells and estrogen-sensitive ZR-75-1 cells. These findings contribute to a better knowledge of the structure of type II 17 beta-HSD and offer an interesting tool to study the regulation of this enzyme in several biological systems. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00260-0

文献信息

• Piperazine derivatives
  申请人：Hoffman-La Roche Inc.

  公开号：US07022707B2

  公开（公告）日：2006-04-04

  The present invention is a chemical compound of formula (I) or a pharmaceutically acceptable salts, solvates and esters thereof, wherein R1 to R4, A1, A2 m and n are as described in the specification.

  本发明是化学式(I)的化合物或其药学上可接受的盐、溶剂合物和酯，其中R1至R4、A1、A2、m和n如规范所述。