6-Bromo-3-(4-fluoro-phenyl)-indan-1-ol | 170380-95-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6-Bromo-3-(4-fluoro-phenyl)-indan-1-ol
• 英文别名: 6-bromo-3-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-ol
• CAS: 170380-95-7
• 化学式: C₁₅H₁₂BrFO
• 分子量: 307.162
• InChiKey: WVAKVIUEIQUPFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-Bromo-3-(4-fluoro-phenyl)-indan-1-ol 在 氯化亚砜 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 18.0h， 生成 1-[6-Bromo-3-(4-fluoro-phenyl)-indan-1-yl]-3,3-dimethyl-piperazine
  参考文献：
  名称：

  Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity

  摘要：

  A study of the effect of aromatic substitution on D-1 and D-2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro- or B-fluoro-substituted derivatives show preference for D-1 receptors. D-1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D-1 and D-2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chlorosubstituted derivatives have potent D-1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED(50) values about 1 mu mol/kg. In vitro all compounds show preference for D-1 receptors, but in vivo they are equally effective as D-1 and D-2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha(1) adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being ''atypical'' antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D-2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D-1 receptor site.

  DOI：

  10.1021/jm00022a004
• 作为产物：
  描述：

  6-Bromo-3-(4-fluoro-phenyl)-indan-1-one 在 sodium tetrahydroborate 作用下， 以90%的产率得到6-Bromo-3-(4-fluoro-phenyl)-indan-1-ol
  参考文献：
  名称：

  Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity

  摘要：

  A study of the effect of aromatic substitution on D-1 and D-2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro- or B-fluoro-substituted derivatives show preference for D-1 receptors. D-1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D-1 and D-2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chlorosubstituted derivatives have potent D-1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED(50) values about 1 mu mol/kg. In vitro all compounds show preference for D-1 receptors, but in vivo they are equally effective as D-1 and D-2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha(1) adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being ''atypical'' antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D-2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D-1 receptor site.

  DOI：

  10.1021/jm00022a004