3-氯-1-(4-氟苯基)-5-(三氟甲基)茚满 | 85118-26-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 3-氯-1-(4-氟苯基)-5-(三氟甲基)茚满
• 中文别名: 3-氯-1-(4-氟苯基)-5-(三氟甲基)-2,3-二氢-1H-茚
• 英文名称: 1-chloro-3-(4-fluorophenyl)-6-(trifluoromethyl)indan
• 英文别名: 3-Chloro-1-(4-fluorophenyl)-5-(trifluoromethyl)indan；3-chloro-1-(4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1H-indene
• CAS: 85118-26-9
• 化学式: C₁₆H₁₁ClF₄
• 分子量: 314.71
• InChiKey: JAHJABLOCCBITR-UHFFFAOYSA-N

物化性质

• 沸点：
  336.9±42.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2903999090

反应信息

• 作为反应物：
  描述：

  3-氯-1-(4-氟苯基)-5-(三氟甲基)茚满 在 lithium aluminium tetrahydride 作用下， 以 乙醚 、 甲苯 、 丁酮 为溶剂， 反应 3.5h， 生成 cis-1-(cyclopropylmethyl)-4-<6-fluoro-3-(4-fluorophenyl)indan-1-yl>piperazine
  参考文献：
  名称：

  Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

  摘要：

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.

  DOI：

  10.1021/jm00361a002
• 作为产物：
  描述：

  2-溴-4-三氟甲基苯甲醛 在 哌啶 、 sodium tetrahydroborate 、 正丁基锂 、 氯化亚砜 、 硫酸 、 magnesium 、 溶剂黄146 作用下， 以 甲醇 、 乙醚 、 正己烷 、 甲苯 为溶剂， 反应 28.0h， 生成 3-氯-1-(4-氟苯基)-5-(三氟甲基)茚满
  参考文献：
  名称：

  Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

  摘要：

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.

  DOI：

  10.1021/jm00361a002

文献信息

• Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity
  作者：Klaus P. Bogeso、Jorn Arnt、Kristen Frederiksen、Hans Otto Hansen、John Hyttel、Henrik Pedersen

  DOI：10.1021/jm00022a004

  日期：1995.10

  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.
• BOGESO, K. P., J. MED. CHEM., 1983, 26, N 7, 935-947
  作者：BOGESO, K. P.

  DOI：——

  日期：——
• VZHUSTOGESPUSTO, K. R.;SNRISTENSEN, A. V.;NUTTEL, J.;LILJEFORS, T., J. MED. CHEM., 1985, 28, N 12, 1817-1828
  作者：VZHUSTOGESPUSTO, K. R.、SNRISTENSEN, A. V.、NUTTEL, J.、LILJEFORS, T.

  DOI：——

  日期：——
• Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans
  作者：Klaus P. Boegesoe

  DOI：10.1021/jm00361a002

  日期：1983.7

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.