3β-(oxycarbonyl(methoxy)acetic acid)-17-(1H-benzimidazol-1-yl)-androsta-5,16-diene | 1441047-10-4

• 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: 3β-(oxycarbonyl(methoxy)acetic acid)-17-(1H-benzimidazol-1-yl)-androsta-5,16-diene
• 英文别名: 2-[2-[[(3S,8R,9S,10R,13S,14S)-17-(benzimidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-2-oxoethoxy]acetic acid
• CAS: 1441047-10-4
• 化学式: C₃₀H₃₆N₂O₅
• 分子量: 504.626
• InChiKey: HYKBTYZJTKWWLZ-JISQPLMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3beta)-17-(1H-苯并咪唑-1-基)雄甾-5,16-二烯-3-醇 3-乙酸酯 在 吡啶 、 4-二甲氨基吡啶 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 4.5h， 生成 3β-(oxycarbonyl(methoxy)acetic acid)-17-(1H-benzimidazol-1-yl)-androsta-5,16-diene
  参考文献：
  名称：

  [EN] ANDROGEN RECEPTOR DOWN-REGULATING AGENTS AND USES THEREOF
  [FR] AGENTS DE DIMINUTION DU RÉCEPTEUR DES ANDROGÈNES ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2014153215A8

文献信息

• Systematic Structure Modifications of Multitarget Prostate Cancer Drug Candidate Galeterone To Produce Novel Androgen Receptor Down-Regulating Agents as an Approach to Treatment of Advanced Prostate Cancer
  作者：Puranik Purushottamachar、Abhijit M. Godbole、Lalji K. Gediya、Marlena S. Martin、Tadas S. Vasaitis、Andrew K. Kwegyir-Afful、Senthilmurugan Ramalingam、Zeynep Ates-Alagoz、Vincent C. O. Njar

  DOI：10.1021/jm400048v

  日期：2013.6.27

  As part of our program to explore the influence of small structural modifications of our drug candidate 3 beta-(hydroxy)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (galeterone, 5) on the modulation of the androgen receptor (AR), we have prepared and evaluated a series of novel C-3, C-16, and C-17 analogues. Using structure activity analysis, we established that the benzimidazole moiety at C-17 is essential and optimal and also that hydrophilic and heteroaromatic groups at C-3 enhance both antiproliferative (AP) and AR degrading (ARD) activities. The most potent antiproliferative compounds were 3 beta-(1H-imidazole-1-carboxylate)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (47), 3-((EZ)-hydroximino)-17-(1H-benzimidazol-1-yl)androsta-4,16-diene (36), and 3 beta-(pyridine-4-carboxylate)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (43), with GI(50) values of 0.87, 1.91, and 2.57 mu M, respectively. Compared to 5, compound 47 was 4- and 8-fold more potent with respect to AP and ARD activities, respectively. Importantly, we also discovered that our compounds, including 5, 36, 43, and 47, could degrade both full-length and truncated ARs in CWR22rv1 human prostate cancer cells. With these activities, they have potential for development as new drugs for the treatment of all forms of prostate cancer.
• [EN] ANDROGEN RECEPTOR DOWN-REGULATING AGENTS AND USES THEREOF<br/>[FR] AGENTS DE DIMINUTION DU RÉCEPTEUR DES ANDROGÈNES ET LEURS UTILISATIONS
  申请人：UNIV MARYLAND

  公开号：WO2014153215A8

  公开（公告）日：2015-11-05