1-bromo-4-methoxy-2,5-dipropylbenzene | 620971-22-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-bromo-4-methoxy-2,5-dipropylbenzene
• CAS: 620971-22-4
• 化学式: C₁₃H₁₉BrO
• 分子量: 271.197
• InChiKey: DVGHWCCVYUIHER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 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：

  1-bromo-4-methoxy-2,5-dipropylbenzene 在 manganese(IV) oxide 、 正丁基锂 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 生成 (2-fluoro-4-methoxyphenyl)(4-methoxy-2,5-dipropylphenyl)methanone
  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：

  1-(甲氧基甲氧基)-3-丙基苯 在 三乙基硅烷 、 N-溴代丁二酰亚胺(NBS) 、 叔丁基锂 、 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 、 正戊烷 为溶剂， 反应 64.5h， 生成 1-bromo-4-methoxy-2,5-dipropylbenzene
  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.