6-bromo-2-methoxy-3-methylnaphthalene | 1285532-62-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-bromo-2-methoxy-3-methylnaphthalene
• CAS: 1285532-62-8
• 化学式: C₁₂H₁₁BrO
• 分子量: 251.123
• InChiKey: JDPXUPIHHRERMB-UHFFFAOYSA-N

物化性质

• 沸点：
  335.4±22.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-bromo-2-methoxy-3-methylnaphthalene 在 吡啶 、 咪唑 、 1,1'-双(二苯基膦)二茂铁 、 正丁基锂 、 四丁基氟化铵 、 palladium diacetate 、 三溴化硼 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -70.0~70.0 ℃ 、101.33 kPa 条件下， 反应 21.16h， 生成 methyl 6-(1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl)-3-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：

  (7-bromo-3-methoxynaphthalen-2-yl)methanol 在 manganese(IV) oxide 、 一水合肼 、 potassium hydroxide 作用下， 以 二氯甲烷 、 三乙二醇 为溶剂， 反应 1.5h， 生成 6-bromo-2-methoxy-3-methylnaphthalene
  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

• Inhibitors of factor Xa
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040116399A1

  公开（公告）日：2004-06-17

  Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

  本发明揭示了一种具有对哺乳动物因子Xa活性的新化合物、其盐和相关组合物。这些化合物在体外或体内用于预防或治疗凝血障碍。
• PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160207936A1

  公开（公告）日：2016-07-21

  Compounds of the formula I or II: wherein X, m, Ar, R 1 and R 2 are as defined herein. The subject compounds are useful for treatment of IRAK-mediated conditions.

  公式I或II的化合物：其中X，m，Ar，R1和R2的定义如下。所述化合物可用于治疗IRAK介导的疾病。
• Pyrazolo[1,5a]pyrimidine derivatives as IRAK4 modulators
  申请人：Hoffmann-La Roche Inc.

  公开号：US10023589B2

  公开（公告）日：2018-07-17

  Compounds of the formula I or II: wherein X, m, Ar, R1 and R2 are as defined herein. The subject compounds are useful for treatment of IRAK-mediated conditions.

  式 I 或 II 的化合物： 其中 X、m、Ar、R1 和 R2 如本文所定义。上述化合物可用于治疗 IRAK 介导的疾病。
• HCV inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：EP2364321B1

  公开（公告）日：2013-04-17
• 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.