3-[(8R,9S,13S,14S,16S,17S)-3-(tert-Butyl-dimethyl-silanyloxy)-13-methyl-17-(tetrahydro-pyran-2-yloxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-propylamine | 387342-82-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-[(8R,9S,13S,14S,16S,17S)-3-(tert-Butyl-dimethyl-silanyloxy)-13-methyl-17-(tetrahydro-pyran-2-yloxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-propylamine
• CAS: 387342-82-7
• 化学式: C₃₂H₅₃NO₃Si
• 分子量: 527.863
• InChiKey: WIBMLWAXQATXFV-LXOUNUAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  37.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  53.71
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-[(8R,9S,13S,14S,16S,17S)-3-(tert-Butyl-dimethyl-silanyloxy)-13-methyl-17-(tetrahydro-pyran-2-yloxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-propylamine 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 反应 26.0h， 生成 (S)-2-Amino-N-[3-((8R,9S,13S,14S,16S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl)-propyl]-3-hydroxy-propionamide; hydrochloride
  参考文献：
  名称：

  Chemical synthesis of 16β-propylaminoacyl derivatives of estradiol and their inhibitory potency on type 1 17β-hydroxysteroid dehydrogenase and binding affinity on steroid receptors

  摘要：

  The 17 beta -hydroxysteroid dehydrogenases (17 beta -HSDs) are members of a family of enzymes that catalyze the interconversion of weakly active sexual hormones (ketosteroids) and potent hormones (17 beta -hydroxysteroids). Among the known isoforms of 17 beta -HSD, the type I catalyzes the NAD(P)H-mediated reduction of estrone (E-1) to estradiol (E-2), a predominant mitogen for the breast cancer cells. Therefore, the inhibition of this particular enzyme is a logical approach to reduce the concentration of estradiol in breast tumors. To develop inhibitors of type 1 17 beta -HSD activity, we hypothesized that molecules containing both hydrophobic and hydrophilic components should be interesting candidates for interacting with both the steroid binding domain and some amino acid residues of the cofactor binding domain of the enzyme. Firstly, a conveniently protected 16 beta-(3-aminopropyl)-E-2 derivative was synthesized from commercially available E-1. Then, a representative of all class of NHBoc-protected amino acids (basic, acid, aromatic, aliphatic, hydroxylated) were coupled using standard procedures to the amino group of the precursor. Finally, cleavage of all protecting groups was performed in a single step to generate a series of 16 beta -propylaminoacyl derivatives of E-2. The enzymatic screenings revealed that none of the novel compounds can inhibit the reductive activity of type 1 17 beta -HSD. On the other hand, all of these E-2 derivatives did not show any significant binding affinity on four steroid receptors including the estrogen receptor. Additional efforts aimed at improving the inhibitory potency of these steroidal derivatives on type 1 17 beta -HSD without providing estrogenic activities is under investigation using a combinatorial chemistry approach. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00116-7
• 作为产物：
  描述：

  [(8R,9S,13S,14S,16S,17S)-16-(3-Azido-propyl)-13-methyl-17-(tetrahydro-pyran-2-yloxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yloxy]-tert-butyl-dimethyl-silane 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 25.0 ℃ 、101.32 kPa 条件下， 反应 16.0h， 以3.4 g的产率得到3-[(8R,9S,13S,14S,16S,17S)-3-(tert-Butyl-dimethyl-silanyloxy)-13-methyl-17-(tetrahydro-pyran-2-yloxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-propylamine
  参考文献：
  名称：

  Chemical synthesis of 16β-propylaminoacyl derivatives of estradiol and their inhibitory potency on type 1 17β-hydroxysteroid dehydrogenase and binding affinity on steroid receptors

  摘要：

  The 17 beta -hydroxysteroid dehydrogenases (17 beta -HSDs) are members of a family of enzymes that catalyze the interconversion of weakly active sexual hormones (ketosteroids) and potent hormones (17 beta -hydroxysteroids). Among the known isoforms of 17 beta -HSD, the type I catalyzes the NAD(P)H-mediated reduction of estrone (E-1) to estradiol (E-2), a predominant mitogen for the breast cancer cells. Therefore, the inhibition of this particular enzyme is a logical approach to reduce the concentration of estradiol in breast tumors. To develop inhibitors of type 1 17 beta -HSD activity, we hypothesized that molecules containing both hydrophobic and hydrophilic components should be interesting candidates for interacting with both the steroid binding domain and some amino acid residues of the cofactor binding domain of the enzyme. Firstly, a conveniently protected 16 beta-(3-aminopropyl)-E-2 derivative was synthesized from commercially available E-1. Then, a representative of all class of NHBoc-protected amino acids (basic, acid, aromatic, aliphatic, hydroxylated) were coupled using standard procedures to the amino group of the precursor. Finally, cleavage of all protecting groups was performed in a single step to generate a series of 16 beta -propylaminoacyl derivatives of E-2. The enzymatic screenings revealed that none of the novel compounds can inhibit the reductive activity of type 1 17 beta -HSD. On the other hand, all of these E-2 derivatives did not show any significant binding affinity on four steroid receptors including the estrogen receptor. Additional efforts aimed at improving the inhibitory potency of these steroidal derivatives on type 1 17 beta -HSD without providing estrogenic activities is under investigation using a combinatorial chemistry approach. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00116-7