6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-1-methyl-2-naphthamide | 337522-91-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-1-methyl-2-naphthamide
• 英文别名: 6-[1-hydroxy-2-methyl-1-(1-tritylimidazol-4-yl)propyl]-N,1-dimethylnaphthalene-2-carboxamide
• CAS: 337522-91-5
• 化学式: C₃₉H₃₇N₃O₂
• 分子量: 579.742
• InChiKey: JYVCVNHEPPNTDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-1-methyl-2-naphthamide 在 吡啶盐酸盐 、 水 、 碳酸氢钠 作用下， 以 甲醇 、 氯仿 为溶剂， 以91%的产率得到6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-1-methyl-2-naphthamide
  参考文献：
  名称：

  17,20-Lyase inhibitors. Part 4: Design, synthesis and structure–activity relationships of naphthylmethylimidazole derivatives as novel 17,20-lyase inhibitors

  摘要：

  A novel series of naphthylmethylimidazole derivatives and related compounds have been investigated as selective 17,20-lyase inhibitors. Optimization of the substituent at the 6-position on the naphthalene ring was performed to yield a methylcarbamoyl derivative, which exhibited potent inhibitory activity against human 17,20-lyase and promising selectivity (> 200-fold) for 17,20-lyase over CYP3A4. Further modifications of the methylcarbamoyl derivative led to the discovery of the corresponding tricyclic compound, which showed highly potent activity against human 17,20-lyase (IC50 19 nM) and good selectivity (> 1000-fold) for inhibition of 17,20-lyase over CYP3A4. Additional biological evaluation revealed that the tricyclic compound had potent in vivo efficacy in monkeys and favorable pharmacokinetic profiles when administered in rats. Asymmetric synthesis of the selective tricyclic inhibitor was also achieved using a chiral alpha-hydroxy ketone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.017
• 作为产物：
  描述：

  methyl-6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-1-methyl-2-naphthoate 在 甲醇 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-1-methyl-2-naphthamide
  参考文献：
  名称：

  17,20-Lyase inhibitors. Part 4: Design, synthesis and structure–activity relationships of naphthylmethylimidazole derivatives as novel 17,20-lyase inhibitors

  摘要：

  A novel series of naphthylmethylimidazole derivatives and related compounds have been investigated as selective 17,20-lyase inhibitors. Optimization of the substituent at the 6-position on the naphthalene ring was performed to yield a methylcarbamoyl derivative, which exhibited potent inhibitory activity against human 17,20-lyase and promising selectivity (> 200-fold) for 17,20-lyase over CYP3A4. Further modifications of the methylcarbamoyl derivative led to the discovery of the corresponding tricyclic compound, which showed highly potent activity against human 17,20-lyase (IC50 19 nM) and good selectivity (> 1000-fold) for inhibition of 17,20-lyase over CYP3A4. Additional biological evaluation revealed that the tricyclic compound had potent in vivo efficacy in monkeys and favorable pharmacokinetic profiles when administered in rats. Asymmetric synthesis of the selective tricyclic inhibitor was also achieved using a chiral alpha-hydroxy ketone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.017

文献信息

• IMIDAZOL-4-YLMETHANOLS USED AS INHIBITORS OF STEROID C17-20 LYASE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1222174B1

  公开（公告）日：2009-05-27
• US6649643B1
  申请人：——

  公开号：US6649643B1

  公开（公告）日：2003-11-18