4,6-dibromo-2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4,6-dibromo-2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol
• 英文别名: 4,6-Dibromo-2-(3-fluoro-4-hydroxyphenyl)-7-vinylbenzo[d]oxazol-5-ol；4,6-dibromo-7-ethenyl-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol
• 化学式: C₁₅H₈Br₂FNO₃
• 分子量: 429.04
• InChiKey: BNIOVAWOIGCLML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-甲氧基-2-硝基酚 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 二氯双(三邻甲苯膦)合钯(II) 、 对二甲苯 、 氢气 、 溴 、 sodium acetate 、 三溴化硼 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙二醇二乙醚 、 乙腈 为溶剂， -78.0~115.0 ℃ 、172.37 kPa 条件下， 反应 72.0h， 生成 4,6-dibromo-2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol
  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

• Prodrug substituted benzoxazoles as estrogenic agents
  申请人：Elmarakby Sayed

  公开号：US20060046968A1

  公开（公告）日：2006-03-02

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

  这项发明提供了具有以下结构的公式I的雌激素受体调节剂，其中Q、Q2、R1、R2、R2a、R3、R3a和X如规范中定义，或其药用可接受盐。
• PHARMACEUTICAL COMPOSITIONS AND METHODS OF PREVENTING, TREATING, OR INHIBITING INFLAMMATORY DISEASES, DISORDERS, OR CONDITIONS OF THE SKIN, AND DISEASES, DISORDERS, OR CONDITIONS ASSOCIATED WITH COLLAGEN DEPLETION
  申请人：CHANG Chien-Neng

  公开号：US20090010884A1

  公开（公告）日：2009-01-08

  The present invention provides compositions and methods for preventing, treating, or inhibiting inflammatory diseases, disorders, or conditions of the skin, and diseases, disorders, or conditions associated with collagen depletion using one or more estrogenic agents.

  本发明提供了使用一个或多个雌激素类药物预防、治疗或抑制皮肤炎症性疾病、紊乱或状况以及与胶原蛋白流失相关的疾病、紊乱或状况的组合物和方法。
• Substituted benzoxazoles as estrogenic agents
  申请人：Wyeth

  公开号：US20030199562A1

  公开（公告）日：2003-10-23

  This invention provides estrogen receptor modulators of formula I, having the structure 1 wherein R 1 , R 2 , R 2a , R 3 , R 3a , and R 4 , and X as defined in the specification, or a pharmaceutically acceptable salt thereof.

  这项发明提供了具有结构1的式I的雌激素受体调节剂，其中R1、R2、R2a、R3、R3a和R4以及规范中定义的X，或其药用可接受盐。
• [EN] SUBSTITUTED BENZOXAZOLES AND ANALOGUES AS ESTROGENIC AGENTS<br/>[FR] BENZOXAZOLES SUBSTITUES ET ANALOGUES UTILISES EN TANT QU'AGENTS OESTROGENES
  申请人：WYETH CORP

  公开号：WO2003050095A1

  公开（公告）日：2003-06-19

  This invention provides estrogen receptor modulators of formula (I), having the structure of formula (I) wherein R1, R2, R2a, R3, R3a, and R4, and X as defined in the specification, or a pharmaceutically acceptable salt thereof.

  本发明提供了公式（I）的雌激素受体调节剂，其具有公式（I）的结构，其中R1、R2、R2a、R3、R3a和R4以及X如规范中定义的，或其药学上可接受的盐。
• PRODRUG SUBSTITUTED BENZOXAZOLES AS ESTROGENIC AGENTS
  申请人：Elmarakby Sayed

  公开号：US20080255057A1

  公开（公告）日：2008-10-16

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

  本发明提供了式I的雌激素受体调节剂，其结构为 其中Q、Q2、R1、R2、R2a、R3、R3a和X如规范中所定义，或其药学上可接受的盐。