6-methoxy-3-(4-methoxy-2-methylphenyl)-1,2-benzisoxazole | 620971-17-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: 6-methoxy-3-(4-methoxy-2-methylphenyl)-1,2-benzisoxazole
• 英文别名: 6-methoxy-3-(4-methoxy-2-methylphenyl)-1,2-benzoxazole
• CAS: 620971-17-7
• 化学式: C₁₆H₁₅NO₃
• 分子量: 269.3
• InChiKey: UREAFHZCFPKVDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  44.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methoxy-3-(4-methoxy-2-methylphenyl)-1,2-benzisoxazole 在 氢碘酸 作用下， 以 乙酸酐 、 溶剂黄146 为溶剂， 反应 2.0h， 以70%的产率得到3-(4-Hydroxy-2-methylphenyl)-1,2-benzisoxazol-6-ol
  参考文献：
  名称：

  Phenyl benzisoxazoles as estrogenic agents

  摘要：

  这项发明提供了式I的雌激素受体调节剂，其具有结构1，其中，R1、R2和R3如规范中定义，或其药用盐。

  公开号：

  US20030207927A1
• 作为产物：
  描述：

  2-溴-5-甲氧基甲苯 在 正丁基锂 、 jones reagent 、 盐酸羟胺 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 7.0h， 生成 6-methoxy-3-(4-methoxy-2-methylphenyl)-1,2-benzisoxazole
  参考文献：
  名称：

  Design and Synthesis of Aryl Diphenolic Azoles as Potent and Selective Estrogen Receptor-β Ligands

  摘要：

  New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are > 100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being >200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least similar to50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.

  DOI：

  10.1021/jm049719y

文献信息

• Phenyl benzisoxazoles as estrogenic agents
  申请人：Wyeth

  公开号：US20030207927A1

  公开（公告）日：2003-11-06

  This invention provides estrogen receptor modulators of formula I, having the structure 1 wherein, R 1 , R 2 , and R 3 are as defined in the specification, or a pharmaceutically acceptable salt thereof.

  这项发明提供了式I的雌激素受体调节剂，其具有结构1，其中，R1、R2和R3如规范中定义，或其药用盐。
• US6884814B2
  申请人：——

  公开号：US6884814B2

  公开（公告）日：2005-04-26
• Design and Synthesis of Aryl Diphenolic Azoles as Potent and Selective Estrogen Receptor-β Ligands
  作者：Michael S. Malamas、Eric S. Manas、Robert E. McDevitt、Iwan Gunawan、Zhang B. Xu、Michael D. Collini、Chris P. Miller、Tam Dinh、Ruth A. Henderson、James C. Keith、Heather A. Harris

  DOI：10.1021/jm049719y

  日期：2004.10.1

  New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are > 100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being >200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least similar to50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.