1-(6-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-2-naphthyl)-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propan-1-ol | 337521-09-2

• 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: 1-(6-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-2-naphthyl)-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propan-1-ol
• 英文别名: 1-(6-tert-butyldimethylsilyloxy-5-methyl-2-naphthyl)-2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanol；1-[6-[Tert-butyl(dimethyl)silyl]oxy-5-methylnaphthalen-2-yl]-2-methyl-1-(1-tritylimidazol-4-yl)propan-1-ol
• CAS: 337521-09-2
• 化学式: C₄₃H₄₈N₂O₂Si
• 分子量: 652.952
• InChiKey: BXVIFBZHBJMDOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.46
• 重原子数：
  48
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(6-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-2-naphthyl)-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propan-1-ol 在 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 四丁基氟化铵 、 palladium diacetate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 16.0h， 生成 methyl-6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-1-methyl-2-naphthoate
  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：

  1-甲基萘-2-醇 在 咪唑 、 正丁基锂 、 溴 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.41h， 生成 1-(6-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-2-naphthyl)-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propan-1-ol
  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-ylmehanols and their use as inhibitors of steroid C17-20 lyase
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06649643B1

  公开（公告）日：2003-11-18

  Imidazol-4-ylmethanols and their uses for preventing and treating primary tumors, metastasis and recurrence of tumors, various symptoms accompanying tumors, prostatic hypertrophy, virilism, hirsutism, male pattern alopecia, precocious puberty, endometriosis, uterine myoma, mastopathy and polycystic ovary syndrome are disclosed.

  Imidazol-4-ylmethanols及其用于预防和治疗原发性肿瘤、肿瘤转移和复发、伴随肿瘤的各种症状、前列腺肥大、男性化、多毛症、男性型脱发、性早熟、子宫内膜异位症、子宫肌瘤、乳腺病和多囊卵巢综合征的用途被披露。
• IMIDAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1344777B1

  公开（公告）日：2011-03-16
• 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.