7-溴-2-(3-氟-4-羟基苯基)-1,3-苯并恶唑-5-醇 | 544704-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 7-溴-2-(3-氟-4-羟基苯基)-1,3-苯并恶唑-5-醇
• 英文名称: 2-(3-Fluoro-4-hydroxyphenyl)-7-bromobenzooxazol-5-ol
• 英文别名: 7-bromo-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol；2-(3-fluoro-4-hydroxyphenyl)-7-bromobenzoxazol-5-ol；7-Bromo-2-(3-fluoro-4-hydroxyphenyl)benzo[d]oxazol-5-ol
• CAS: 544704-73-6
• 化学式: C₁₃H₇BrFNO₃
• 分子量: 324.106
• InChiKey: GGHZQYDERZQJFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  1
• 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

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C，干燥密封保存。

反应信息

• 作为反应物：
  描述：

  7-溴-2-(3-氟-4-羟基苯基)-1,3-苯并恶唑-5-醇 在 1,4-二氧六环 、 4-二甲氨基吡啶 、 二氯双(三邻甲苯膦)合钯(II) 作用下， 以 乙二醇二乙醚 为溶剂， 反应 96.0h， 生成 4-[5-(acetyloxy)-1,3-benzoxazol-2-yl]-7-vinyl-2-fluorophenyl acetate
  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
• 作为产物：
  描述：

  4-甲氧基-2-硝基酚 在 吡啶 、 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 为溶剂， -78.0~70.0 ℃ 、172.37 kPa 条件下， 反应 8.0h， 生成 7-溴-2-(3-氟-4-羟基苯基)-1,3-苯并恶唑-5-醇
  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

• [EN] PHOSPHATE DERIVATIVES OF SUBSTITUTED BENZOXAZOLES<br/>[FR] DÉRIVÉS PHOSPHATE DE BENZOXAZOLES SUBSTITUÉS
  申请人：WYETH CORP

  公开号：WO2009100335A1

  公开（公告）日：2009-08-13

  The present invention relates to phosphate derivatives of estrogen receptor beta agonists, compositions thereof, preparations thereof, and uses thereof. Formula (I).

  本发明涉及雌激素受体β激动剂的磷酸酯衍生物，其组成物，制备物和用途。公式（I）。
• 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。
• Process for the purification of substituted benzoxazole compounds
  申请人：Iera Silvio

  公开号：US20060199967A1

  公开（公告）日：2006-09-07

  The present invention provides processes for the purification of substituted benzoxazole compounds, and in particular 2-(3-fluoro-4-hydroxy-phenyl)-7-vinyl-benzooxazol-5-ol. The processes include recrystallizing the compound from a solution comprising acetone and acetonitrile; treating the crude purified product with a clarifying agent in a solution comprising ethyl acetate, and precipitating or triturating the compound from a mixed solvent system.

  本发明提供了用于纯化取代苯并噁唑化合物的工艺，特别是2-(3-氟-4-羟基苯基)-7-乙烯基苯并噁唑-5-醇。该工艺包括从包含丙酮和乙腈的溶液中再结晶该化合物；用澄清剂处理粗纯化产物，溶解于乙酸乙酯的溶液中，并从混合溶剂系统中沉淀或粉碎该化合物。