16α-(4-azido-2-butynyl)-3-t-butyldimethylsilyloxyestra-1,3,5(10)-trien-17-one | 119542-59-5

• 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: 16α-(4-azido-2-butynyl)-3-t-butyldimethylsilyloxyestra-1,3,5(10)-trien-17-one
• CAS: 119542-59-5
• 化学式: C₂₈H₃₉N₃O₂Si
• 分子量: 477.722
• InChiKey: GWGYXUMUUHQRBS-APSGYHDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.43
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  75.06
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  16α-(4-azido-2-butynyl)-3-t-butyldimethylsilyloxyestra-1,3,5(10)-trien-17-one 在 lithium aluminium tetrahydride 、 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of geldanamycin-estradiol hybrids

  摘要：

  Geldanamycin (GDM) binds to the Hsp90 chaperone protein and causes the degradation of several important signalling proteins. A series of novel estradiol-geldanamycin hybrids has been synthesized and evaluated for their ability to induce the selective degradation of the estrogen receptor (ER). The hybrid compounds are active and more selective than the parent causing degradation of ER and HER2, but not other GDM targets. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00185-7
• 作为产物：
  描述：

  3-(O-tert-butyl(dimethyl)silyl)estrone 在 sodium azide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 12.0h， 生成 16α-(4-azido-2-butynyl)-3-t-butyldimethylsilyloxyestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Synthesis and evaluation of geldanamycin-estradiol hybrids

  摘要：

  Geldanamycin (GDM) binds to the Hsp90 chaperone protein and causes the degradation of several important signalling proteins. A series of novel estradiol-geldanamycin hybrids has been synthesized and evaluated for their ability to induce the selective degradation of the estrogen receptor (ER). The hybrid compounds are active and more selective than the parent causing degradation of ER and HER2, but not other GDM targets. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00185-7

文献信息

• Estrogen receptor binding tolerance of 16α-substituted estradiol derivatives
  作者：Thomas L. Fevig、Michael K. Mao、John A. Katzenellenbogen

  DOI：10.1016/0039-128x(88)90046-3

  日期：1988.5

  In order to examine the tolerance of the estrogen receptor for 16 alpha-substituents in estradiol, we have synthesized various 16 alpha-substituted estrogens and determined their binding affinity for receptor by a competitive radiometric binding assay. The substituents ranged from small, single-atom substituents (halogens), two-atom substituents (halomethyl groups), to larger alkyl groups and ultimately alkyl groups bearing various functionality, including fluorescent (nitrobenzoxadiazole, NBD) and photoreactive (nitroazidophenyl, NAP) groups. The estrogen receptor seems to have a moderate tolerance for bulky substituents: All of the halogen and halomethyl substituents bind with an affinity at least 50% that of estradiol; in the three atom alkyl series, the affinity declined markedly from propargyl (44%) and allyl (38%) to propyl (5%), suggestive of detailed steric constraints or a preference for unsaturation. The larger, more highly functionalized derivatives ranged in affinity from 0.1-7%, with the highest affinity binders being benzyl (5%) and 4-phenoxy-2(E)-butenyl (7%); most of the lowest affinity ones were the bulky fluorescent and photoreactive derivatives. Thus, the estrogen receptor has good tolerance for estradiol derivatives substituted at the 16 alpha-position with nonpolar groups of moderate bulk; however, with groups of larger bulk, affinity is much lower and becomes highly dependent upon the polarity and detailed structure of the substituents.