N-{6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]naphthalen-2-yl}-N'-methylurea | 1285532-61-7

• 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: N-{6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]naphthalen-2-yl}-N'-methylurea
• 英文别名: 1-[6-[1-Hydroxy-2-methyl-1-(1-tritylimidazol-4-yl)propyl]naphthalen-2-yl]-3-methylurea
• CAS: 1285532-61-7
• 化学式: C₃₈H₃₆N₄O₂
• 分子量: 580.729
• InChiKey: VWUURNQUOYVKCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  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：
  0.16
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-{6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]naphthalen-2-yl}-N'-methylurea 在 吡啶盐酸盐 、 水 、 碳酸氢钠 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 3.0h， 以278 mg的产率得到N'-{6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthyl}-N-methylurea
  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：

  2,6-二溴萘 在 吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 盐酸羟胺 、 sodium acetate 、 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 甲苯 为溶剂， 反应 21.17h， 生成 N-{6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]naphthalen-2-yl}-N'-methylurea
  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

• Naphthalene derivatives, their production and use
  申请人：——

  公开号：US20030236274A1

  公开（公告）日：2003-12-25

  A composition containing a compound of the formula: 1 wherein A is a nitrogen-containing heterocyclic group which may be substituted, R 1 is a hydrogen atom, hydrocarbon group which may be substituted, or monocyclic aromatic heterocyclic group which may be substituted, R 2 is a hydrogen atom or a lower alkyl group which may be substituted, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently a hydrogen atom, a hydrocarbon group which may be substituted, a hydroxy group which may be substituted, a thiol group which may be substituted, an amino group which may be substituted, an acyl group or a halogen atom, a salt thereof or a prodrug thereof has steroid C 17,20 -lyase inhibitory activity, and are useful for preventing and treating a mammal suffering from, for example, primary cancer of malignant tumor, its metastasis and recurrence thereof.

  一种含有化合物的组合物，该化合物的分子式为：1其中A是一种含氮杂环基团，可以被取代，R1是氢原子、可以被取代的碳氢基团或可以被取代的单环芳杂环基团，R2是氢原子或可以被取代的低碳基基团，R3、R4、R5、R6、R7、R8和R9分别为氢原子、可以被取代的碳氢基团、可以被取代的羟基、可以被取代的硫醇基、可以被取代的氨基、酰基或卤素原子，它们的盐或前药具有类固醇C17,20-裂解酶抑制活性，并且可用于预防和治疗患有例如恶性肿瘤的原发性癌症、其转移和复发的哺乳动物。
• NAPHTHALENE DERIVATIVES, THEIR PRODUCTION AND USE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1073640B1

  公开（公告）日：2005-04-13
• US6573289B1
  申请人：——

  公开号：US6573289B1

  公开（公告）日：2003-06-03
• US7084149B2
  申请人：——

  公开号：US7084149B2

  公开（公告）日：2006-08-01
• 17,20-Lyase inhibitors. Part 4: Design, synthesis and structure–activity relationships of naphthylmethylimidazole derivatives as novel 17,20-lyase inhibitors
  作者：Tomohiro Kaku、Nobuyuki Matsunaga、Akio Ojida、Toshimasa Tanaka、Takahito Hara、Masuo Yamaoka、Masami Kusaka、Akihiro Tasaka

  DOI：10.1016/j.bmc.2011.01.017

  日期：2011.3

  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.