3,17-bis-O-(tert-butyldimethylsilyl)-2-(1-propynyl)estradiol | 192062-01-4

• 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: 3,17-bis-O-(tert-butyldimethylsilyl)-2-(1-propynyl)estradiol
• 英文别名: 3,17β-bis[(tert-butyldimethylsilyl)oxy]-2-(1-propynyl)-1,3,5(10)-estratriene；tert-butyl-[[(8R,9S,13S,14S,17S)-3-[tert-butyl(dimethyl)silyl]oxy-13-methyl-2-prop-1-ynyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]oxy]-dimethylsilane
• CAS: 192062-01-4
• 化学式: C₃₃H₅₄O₂Si₂
• 分子量: 538.962
• InChiKey: NWVOLQUOTRHZQV-XDWNBPONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.69
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,17-bis-O-(tert-butyldimethylsilyl)-2-(1-propynyl)estradiol 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 以86%的产率得到2-(1'-propynyl)estradiol
  参考文献：
  名称：

  The Effect of Exchanging Various Substituents at the 2-Position of 2-Methoxyestradiol on Cytotoxicity in Human Cancer Cell Cultures and Inhibition of Tubulin Polymerization

  摘要：

  A new set of estradiol derivatives bearing various substituents at the 2-position were synthesized in order to further elucidate the structural parameters associated with the antitubulin activity and cytotoxicity of 2-substituted estradiols. The potencies of the new compounds as inhibitors of tubulin polymerization were determined, and the cytotoxicities of the analogues in human cancer cell cultures were investigated. The substituents introduced into the 2-position of estradiol included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, 3-N,N-dimethylaminoethylideneamino, 2'-hydroxyethylineneamino, (beta-3,4,5-trimethoxyphenyl)ethenyl, phenylethynyl, ethynly, 1'-propynyl, and cyano. The substituents conferring the ability to inhibit tubulin polymerization included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, ethynyl, and 1'-propynyl. The remaining compounds were all inactive as inhibitors of tubulin polymerization when tested at concentrations of up to 40 muM. All of the compounds were cytotoxic in a panel of 55 human cancer cell cultures, and in general, the most cytotoxic compounds were also the most potent as inhibitors of tubulin polymerization. 2-(1'-Propynyl)estradiol displayed significant anticancer activity in the in vivo hollow fiber animal model.

  DOI：

  10.1021/jm020218r
• 作为产物：
  描述：

  1-丙炔溴化镁 、 3,17-bis-O-(tert-butyldimethylsilyl)-2-iodo-estradiol 在 zinc dibromide 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 反应 6.17h， 以82%的产率得到3,17-bis-O-(tert-butyldimethylsilyl)-2-(1-propynyl)estradiol
  参考文献：
  名称：

  The Effect of Exchanging Various Substituents at the 2-Position of 2-Methoxyestradiol on Cytotoxicity in Human Cancer Cell Cultures and Inhibition of Tubulin Polymerization

  摘要：

  A new set of estradiol derivatives bearing various substituents at the 2-position were synthesized in order to further elucidate the structural parameters associated with the antitubulin activity and cytotoxicity of 2-substituted estradiols. The potencies of the new compounds as inhibitors of tubulin polymerization were determined, and the cytotoxicities of the analogues in human cancer cell cultures were investigated. The substituents introduced into the 2-position of estradiol included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, 3-N,N-dimethylaminoethylideneamino, 2'-hydroxyethylineneamino, (beta-3,4,5-trimethoxyphenyl)ethenyl, phenylethynyl, ethynly, 1'-propynyl, and cyano. The substituents conferring the ability to inhibit tubulin polymerization included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, ethynyl, and 1'-propynyl. The remaining compounds were all inactive as inhibitors of tubulin polymerization when tested at concentrations of up to 40 muM. All of the compounds were cytotoxic in a panel of 55 human cancer cell cultures, and in general, the most cytotoxic compounds were also the most potent as inhibitors of tubulin polymerization. 2-(1'-Propynyl)estradiol displayed significant anticancer activity in the in vivo hollow fiber animal model.

  DOI：

  10.1021/jm020218r

文献信息

• Pd(0)-Mediated Cross Coupling of 2-Iodoestradiol with Organozinc Bromides: A General Route to the Synthesis of 2-Alkynyl, 2-Alkenyl and 2-Alkylestradiol Analogs
  作者：Arasambattu K. Mohanakrishnan、Mark Cushman

  DOI：10.1055/s-1999-2773

  日期：1999.7
• Synthesis of Analogs of 2-Methoxyestradiol with Enhanced Inhibitory Effects on Tubulin Polymerization and Cancer Cell Growth
  作者：Mark Cushman、Hu-Ming He、John A. Katzenellenbogen、Ravi K. Varma、Ernest Hamel、Chii M. Lin、Siya Ram、Yesh P. Sachdeva

  DOI：10.1021/jm9700833

  日期：1997.7.1

  A new series of estradiol analogs was synthesized in an attempt to improve on the anticancer activity of 2-methoxyestradiol, a naturally occurring mammalian tubulin polymerization inhibitor. The compounds were evaluated as inhibitors of tubulin polymerization and the binding of [H-3]colchicine to tubulin, as well as for in vitro cytotoxicity in human cancer cell cultures. Overall, the most potent of the new compounds were 2-(2',2',2'-trifluoroethoxy)-6-oximinoestradiol, 2-ethoxy-6-oximinoestradiol, and 2-ethoxy-6-methoximinoestradiol. These agents lacked significant affinity for the estrogen receptor. The cytotoxicities of the compounds correlated in general with their abilities to inhibit tubulin polymerization, thus supporting inhibition of tubulin polymerization as the primary mechanism causing inhibition of cell growth.
• The Effect of Exchanging Various Substituents at the 2-Position of 2-Methoxyestradiol on Cytotoxicity in Human Cancer Cell Cultures and Inhibition of Tubulin Polymerization
  作者：Mark Cushman、Arasambattu K. Mohanakrishnan、Melinda Hollingshead、Ernest Hamel

  DOI：10.1021/jm020218r

  日期：2002.10.1

  A new set of estradiol derivatives bearing various substituents at the 2-position were synthesized in order to further elucidate the structural parameters associated with the antitubulin activity and cytotoxicity of 2-substituted estradiols. The potencies of the new compounds as inhibitors of tubulin polymerization were determined, and the cytotoxicities of the analogues in human cancer cell cultures were investigated. The substituents introduced into the 2-position of estradiol included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, 3-N,N-dimethylaminoethylideneamino, 2'-hydroxyethylineneamino, (beta-3,4,5-trimethoxyphenyl)ethenyl, phenylethynyl, ethynly, 1'-propynyl, and cyano. The substituents conferring the ability to inhibit tubulin polymerization included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, ethynyl, and 1'-propynyl. The remaining compounds were all inactive as inhibitors of tubulin polymerization when tested at concentrations of up to 40 muM. All of the compounds were cytotoxic in a panel of 55 human cancer cell cultures, and in general, the most cytotoxic compounds were also the most potent as inhibitors of tubulin polymerization. 2-(1'-Propynyl)estradiol displayed significant anticancer activity in the in vivo hollow fiber animal model.