4-((1S,3R)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 4-((1S,3R)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine
• 英文别名: 4-[(1S,3R)-6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-yl]-1,2,2-trimethylpiperazine
• 化学式: C₂₂H₂₇ClN₂
• 分子量: 354.923
• InChiKey: BYPMJBXPNZMNQD-CTNGQTDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-((1S,3R)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine 生成 齐洛那平
  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：

  2,2-二甲基-1,2,5,6-四氢吡嗪 在 palladium on activated charcoal 甲酸 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 20.0h， 生成 4-((1S,3R)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-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

文献信息

• [EN] SUCCINATE AND MALONATE SALT OF TRANS-4-(IR,3S)-6-CHLORO-3-PHENYLINDAN-1-YL)-1,2,2-TRIMETHYLPIPERAZINE AND THE USE AS A MEDICAMENT<br/>[FR] SEL DE SUCCINATE ET DE MALONATE DE TRANS-4-((1R,3S)-6-CHLORO-3-PHENYLINDAN-1-YL)-1,2,2-TRIMETHYLPIPERAZINE ET SON UTILISATION EN TANT QUE MEDICAMENT
  申请人：LUNDBECK & CO AS H

  公开号：WO2005016900A1

  公开（公告）日：2005-02-24

  4-((1R,3S)-6-Chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine hydrogen succinate or hadrogen malonat, pharmaceutical compositions containing these salts and the medical use thereof, including for the treatment of schizophrenia and other psychotic disorders. Also described are methods for the preparation of 4-((1R,3S)-6-Chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and medical uses thereof.

  4-((1R,3S)-6-氯-3-苯基茚-1-基)-1,2,2-三甲基哌嗪氢丁二酸盐或氢丁二酸盐，含有这些盐的药物组合物及其医疗用途，包括用于治疗精神分裂症和其他精神疾病。还描述了制备4-((1R,3S)-6-氯-3-苯基茚-1-基)-1,2,2-三甲基哌嗪和其医疗用途的方法。
• [EN] METHOD FOR RESOLUTION OF 4-((1R,3S)-6-CHLORO-3-PHENYL-INDAN-1-YL)-1,2,2-TRIMETHYL-PIPERAZINE AND 1-((1R,3S)-6-CHLORO-3-PHENYL-INDAN, 1-YL)-3,3-DIMETHYL-PIPERAZINE<br/>[FR] PROCÉDÉ DE DÉDOUBLEMENT DE LA 4-((1R,3S)-6-CHLORO-3-PHÉNYL-INDAN-1-YL)- 1,2,2-TRIMÉTHYL-PIPÉRAZINE ET DE LA 1-((1R,3S)-6-CHLORO-3-PHÉNYL-INDAN- 1-YL)-3,3-DIMÉTHYL-PIPÉRAZINE
  申请人：LUNDBECK & CO AS H

  公开号：WO2012093165A1

  公开（公告）日：2012-07-12

  The present invention relates to resolution methods for manufacture of 4-((1R,3S)-6- chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine and 1-((1R,3S)-6-chloro-3- phenyl-indan-1-yl)-3,3-dimethyl-piperazine and pharmaceutically acceptable salts thereof.

  本发明涉及用于制造4-((1R,3S)-6-氯-3-苯基-茚-1-基)-1,2,2-三甲基哌嗪和1-((1R,3S)-6-氯-3-苯基-茚-1-基)-3,3-二甲基哌嗪及其药学上可接受的盐的分辨方法。
• [EN] MANUFACTURE OF 4-((1R,3S)-6-CHLORO-3-PHENYL-INDAN-1-YL)-1,2,2-TRIMETHYL-PIPERAZINE AND 1-((1R,3S)-6-CHLORO-3-PHENYL-INDAN-1-YL)-3,3-DIMETHYL-PIPERAZINE<br/>[FR] FABRICATION DE LA 4-((1R,3S)-6-CHLORO-3-PHÉNYL-INDAN-1-YLE)-1,2,2-TRIMÉTHYL-PIPÉRAZINE ET DE LA 1-((1R,3S)-6-CHLORO-3-PHÉNYL-INDAN-1-YLE)-3,3-DIMÉTHYL-PIPÉRAZINE
  申请人：LUNDBECK & CO AS H

  公开号：WO2011003423A1

  公开（公告）日：2011-01-13

  The present invention relates to a process for the manufacture of 4-((1R,3S)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine or a pharmaceutically acceptable salt thereof and a process for the manufacture of 1-((1R,3S)-6-Chloro-3-phenyl-indan-1-yl)-3,3-dimethyl-piperazine or a pharmaceutically acceptable salt thereof.

  本发明涉及制备4-((1R,3S)-6-氯-3-苯基-茚烷-1-基)-1,2,2-三甲基哌嗪或其药学上可接受的盐的方法，以及制备1-((1R,3S)-6-氯-3-苯基-茚烷-1-基)-3,3-二甲基哌嗪或其药学上可接受的盐的方法。
• Succinate and malonate salt of trans 4-(ir,3s)-6-chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and the use as a medicament
  申请人：de Diego Lopez Heidi

  公开号：US20060281759A1

  公开（公告）日：2006-12-14

  4-((1R,3S)-6-Chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine hydrogen succinate or hydrogen malonate, pharmaceutical compositions containing these salts and the medical use thereof, including for the treatment of schizophrenia and other psychotic disorders. Also described are methods for the preparation of 4-((1R,3S)-6-Chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and medical uses thereof.

  4-((1R,3S)-6-氯-3-苯基茚烷-1-基)-1,2,2-三甲基哌嗪氢琥珀酸盐或琥珀酸盐，含有这些盐的医药组合物及其医疗用途，包括用于治疗精神分裂症和其他精神疾病。还描述了4-((1R,3S)-6-氯-3-苯基茚烷-1-基)-1,2,2-三甲基哌嗪及其医疗用途的制备方法。
• MALONATE SALT OF 4-((1R,3S)-6-CHLORO-3-PHENYLINDAN-1-YL)-1,2,2-TRIMETHYLPIPERAZINE AND USES OF SAME
  申请人：Lopez de Diego Heidi

  公开号：US20110053957A1

  公开（公告）日：2011-03-03

  4-((1R,35)-6-Chloro-3 -phenylindan-1-yl)-1,2,2-trimethylpiperazine hydrogen malonate salt and pharmaceutical comprising and uses of the same, including for the treatment of schizophrenia and other psychotic disorders are described.

  本文描述了4-((1R,35)-6-氯-3-苯基茚并[1,2-b]噻吩-1-基)-1,2,2-三甲基哌嗪盐酸马来酸盐及其制药用途，包括治疗精神分裂症和其他精神疾病。