3β-acetoxy-17-(1H-benzimidazol-1-yl)-16-((isopentylamino)methyl)-androsta-5,16-diene | 1441046-89-4

• 分子结构分类: 有机化合物
• 英文名称: 3β-acetoxy-17-(1H-benzimidazol-1-yl)-16-((isopentylamino)methyl)-androsta-5,16-diene
• 英文别名: [(3S,8R,9S,10R,13S,14S)-17-(benzimidazol-1-yl)-10,13-dimethyl-16-[(3-methylbutylamino)methyl]-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• CAS: 1441046-89-4
• 化学式: C₃₄H₄₇N₃O₂
• 分子量: 529.766
• InChiKey: KQGFWUIFLQLRMN-RSDCQRSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-acetoxy-17-(1H-benzimidazol-1-yl)-16-((isopentylamino)methyl)-androsta-5,16-diene 在 甲醇 、 potassium hydroxide 作用下， 反应 3.0h， 以0.065 g的产率得到3β-hydoxy-17-(1H-benzimidazol-1-yl)-16-((isopentylamino)-methyl)androsta-5,16-diene
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm400048v
• 作为产物：
  描述：

  (3beta)-3-(乙酰氧基)-17-(1H-苯并咪唑-1-基)雄甾-5,16-二烯-16-甲醛 在 sodium tetrahydroborate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 4.5h， 生成 3β-acetoxy-17-(1H-benzimidazol-1-yl)-16-((isopentylamino)methyl)-androsta-5,16-diene
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm400048v

文献信息

• ANDROGEN RECEPTOR DOWN-REGULATING AGENTS AND USES THEREOF
  申请人：UNIVERSITY OF MARYLAND EASTERN SHORE

  公开号：US20150361126A1

  公开（公告）日：2015-12-17

  The present disclosure provides the design and synthesis of novel steroidal compounds that cause down-regulation of the androgen receptor (AR), both full length and splice variant. The compounds are potential agents for the treatment of all forms of prostate cancer and other diseases that depend on functional AR.

  本公开说明提供了新型类固醇化合物的设计和合成，这些化合物可以导致雄激素受体（AR）的下调，包括全长和剪切变异体。这些化合物是治疗各种前列腺癌和其他依赖于功能性AR的疾病的潜在药物。
• [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
• US9439912B2
  申请人：——

  公开号：US9439912B2

  公开（公告）日：2016-09-13
• US9884067B2
  申请人：——

  公开号：US9884067B2

  公开（公告）日：2018-02-06