2-nitro-3-O-(tert-butyldimethylsilyl)estrone | 165619-18-1

• 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: 2-nitro-3-O-(tert-butyldimethylsilyl)estrone
• 英文别名: 3-(Tert-butyldimethylsilyloxy)-2-nitro-1,3,5(10)-estratrien-17-one；3-tert-Butyldimethylsilyloxy-2-nitroestra-1,3,5(10)-trien-17-one；(8R,9S,13S,14S)-3-[tert-butyl(dimethyl)silyl]oxy-13-methyl-2-nitro-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 165619-18-1
• 化学式: C₂₄H₃₅NO₄Si
• 分子量: 429.632
• InChiKey: YARKNVQPMYWGRX-MIVVTYSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-nitro-3-O-(tert-butyldimethylsilyl)estrone 在 palladium on activated charcoal 吡啶 、 sodium tetrahydroborate 、 四丁基氟化铵 、 氢气 作用下， 以 四氢呋喃 为溶剂， 25.0 ℃ 、137.9 kPa 条件下， 反应 49.17h， 生成 2-Acetamidoestradiol
  参考文献：
  名称：

  Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogs of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite of Estradiol That Inhibits Tubulin Polymerization by Binding to the Colchicine Binding Site

  摘要：

  In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.

  DOI：

  10.1021/jm00012a003
• 作为产物：
  描述：

  雌酚酮 在 咪唑 、 硝酸 作用下， 以 溶剂黄146 为溶剂， 反应 24.5h， 生成 2-nitro-3-O-(tert-butyldimethylsilyl)estrone
  参考文献：
  名称：

  Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogs of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite of Estradiol That Inhibits Tubulin Polymerization by Binding to the Colchicine Binding Site

  摘要：

  In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.

  DOI：

  10.1021/jm00012a003

文献信息

• Inhibitors of type 5 and type 3 17&bgr;-hydroxysteroid dehydrogenase and methods for their use
  申请人：Endorecherche, Inc.

  公开号：US06541463B1

  公开（公告）日：2003-04-01

  Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17&bgr;-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17&bgr;-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17&bgr;-hydroxysteroid dehydrogenase.

  揭示了针对对雄激素或雌激素活性敏感的疾病的医疗治疗和/或抑制疾病发展的新方法。这些治疗方法利用了5型和/或3型17β-羟基类固醇脱氢酶的抑制剂。还披露了新型的5型17β-羟基类固醇脱氢酶抑制剂，以及新型的3型17β-羟基类固醇脱氢酶抑制剂。
• Inhibitors of type 5 and type 3 17beta-hydroxysteroid dehydrogenase and methods for their use
  申请人：Endorecherche, Inc.

  公开号：US20040082556A1

  公开（公告）日：2004-04-29

  Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17&bgr;-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17&bgr;-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17&bgr;-hydroxysteroid dehydrogenase.

  本发明揭示了一种针对对雄激素或雌激素活性敏感的疾病的新型医疗治疗和/或抑制疾病发展的方法。这些治疗方法利用了类型5和/或类型3的17β-羟基类固醇脱氢酶的抑制剂。本发明还揭示了新型的类型5 17β-羟基类固醇脱氢酶抑制剂，以及新型的类型3 17β-羟基类固醇脱氢酶抑制剂。
• Estrone sulfamate inhibitors of estrone sulfatase, and associated
  申请人：SRI International

  公开号：US06046186A1

  公开（公告）日：2000-04-04

  Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) wherein r1 is an optional double bond, R.sup.1 and R.sup.2 are selected from the group consisting of hydrogen and lower alky, or together form a cyclic substituent (II) ##STR1## wherein Q is NH, O or CH.sub.2, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

  提供了可用作雌酮硫酸酯酶抑制剂的新化合物。这些化合物具有结构式（I），其中r1是可选的双键，R.sup.1和R.sup.2选择自氢和较低的烷基，或者一起形成一个环状取代基（II）##STR1##其中Q为NH，O或CH.sub.2，其他各种取代基如此处所定义。还提供了制药组合物和使用公式（I）的化合物治疗雌激素依赖性疾病的方法。
• Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogs of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite of Estradiol That Inhibits Tubulin Polymerization by Binding to the Colchicine Binding Site
  作者：Mark Cushman、Hu-Ming He、John A. Katzenellenbogen、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00012a003

  日期：1995.6

  In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.