(8R,9S,10R,13S,14S,17S)-17-(8-Amino-oct-1-ynyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one | 216064-09-4

• 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: (8R,9S,10R,13S,14S,17S)-17-(8-Amino-oct-1-ynyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one
• 英文别名: (8R,9S,10R,13S,14S,17S)-17-(8-aminooct-1-ynyl)-17-hydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 216064-09-4
• 化学式: C₂₇H₄₁NO₂
• 分子量: 411.628
• InChiKey: RQYUMFRUWDNHPV-AIFRIFMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (8R,9S,10R,13S,14S,17S)-17-(8-Amino-oct-1-ynyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one 、 geldanamycin 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of geldanamycin–testosterone hybrids

  摘要：

  Geldanamycin (GDM) binds to the Hsp90 chaperone protein resulting in the degradation of several important signaling proteins. A series of GDM-testosterone linked hybrids has been synthesized and evaluated for activity against prostate cancer cell lines. The hybrid with the greatest activity exhibits potent and selective cytotoxicity against prostate cancer cells containing the androgen receptor. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00208-0
• 作为产物：
  描述：

  (8'R,9'S,10'R,13'S,14'S,17'S)-17'-(8-azidooct-1-ynyl)-10',13'-dimethylspiro[1,3-dioxolane-2,3'-2,4,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene]-17'-ol 在 盐酸 、 甲醇 、 水 、 三乙基膦 作用下， 以 四氢呋喃 为溶剂， 生成 (8R,9S,10R,13S,14S,17S)-17-(8-Amino-oct-1-ynyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one
  参考文献：
  名称：

  Synthesis and evaluation of geldanamycin–testosterone hybrids

  摘要：

  Geldanamycin (GDM) binds to the Hsp90 chaperone protein resulting in the degradation of several important signaling proteins. A series of GDM-testosterone linked hybrids has been synthesized and evaluated for activity against prostate cancer cell lines. The hybrid with the greatest activity exhibits potent and selective cytotoxicity against prostate cancer cells containing the androgen receptor. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00208-0

文献信息

• METHODS AND COMPOSITIONS FOR DESTRUCTION OF SELECTED PROTEINS
  申请人：Sloan-Kettering InstituteFor Cancer Research

  公开号：EP1023315A1

  公开（公告）日：2000-08-02
• EP1023315A4
  申请人：——

  公开号：EP1023315A4

  公开（公告）日：2004-12-29
• US6670348B1
  申请人：——

  公开号：US6670348B1

  公开（公告）日：2003-12-30
• [EN] METHODS AND COMPOSITIONS FOR DESTRUCTION OF SELECTED PROTEINS<br/>[FR] METHODES ET COMPOSITIONS DE DESTRUCTION DE PROTEINES SELECTIONNEES
  申请人：SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH

  公开号：WO1998051702A1

  公开（公告）日：1998-11-19

  (EN) Compounds having an ansamycin antibiotic, or other moiety which binds to hsp90, coupled to a targeting moiety which binds specifically to a protein, receptor or marker can provide effective targeted delivery of the ansamycin antibiotic leading to the degradation of proteins and death of the targeted cells. These compositions may have different specificity than the ansamycin alone, allowing for a more specific targeting of the therapy, and can be effective in instances where the ansamycin alone has no effect. Thus, these compounds provide an entirely new class of targeted chemotherapy agents with application, depending on the nature of the targeting moiety, to treatment of a variety of different forms of cancer. Such agents can further be used to promote selective degradation of proteins associated with the pathogenesis of other diseases, including antigens associated with autoimmune disorders and pathogenic proteins associated with Alzheimer's disease. Exemplary targeting moieties which may be employed in compounds of the invention include testosterone, estradiol, tamoxifen and wortmannin.(FR) L'invention concerne des composés comprenant un antibiotique d'ansamycine ou une autre fraction se liant à hsp90, couplés à une fraction cible qui se lie spécifiquement à une protéine, un récepteur ou un marqueur, et capables de favoriser une libération ciblée effective de l'antibiotique d'ansamycine entraînant la dégradation de protéines et la mort des cellules ciblées. Ces compositions peuvent présenter des particularités différentes de celles de l'ansamycine seule, ce qui permet un ciblage plus spécifique du traitement, et elles peuvent être efficaces dans des cas où l'ansamycine seule n'a pas d'effet. Ainsi, ces composés forment une classe entièrement nouvelle d'agents chimiothérapeutiques ciblés avec application, selon la nature de la fraction de ciblage, au traitement de plusieurs formes différentes de cancers. De tels agents peuvent également s'utiliser pour favoriser une dégradation sélective de protéines associées à la pathogenèse d'autres affections, y compris des antigènes associés à des troubles auto-immunes et des protéines pathogènes associées à la maladie d'Alzheimer. Des fractions de ciblage pouvant s'utiliser dans des composés de l'invention comprennent par exemple, du testostérone, de l'oestradiol, du tamoxifène et de la wortmannine.