6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-ol | 170380-92-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-ol
• CAS: 170380-92-4
• 化学式: C₁₅H₁₃ClO
• 分子量: 244.721
• InChiKey: NVZAYUDBSXWJKD-UHFFFAOYSA-N

物化性质

• 沸点：
  383.3±42.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 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：
  1

反应信息

• 作为反应物：
  描述：

  6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-ol 在 甲酸 、 氯化亚砜 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 20.0h， 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：

  6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-one 在 sodium tetrahydroborate 作用下， 以88%的产率得到6-chloro-3-phenyl-2,3-dihydro-1H-inden-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

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。
• DEUTERATED 1-PIPERAZINO-3-PHENYL-INDANES FOR TREATMENT OF SCHIZOPHRENIA
  申请人：JORGENSEN Morten

  公开号：US20120322811A1

  公开（公告）日：2012-12-20

  The present invention relates to deuterated 1-piperazino-3-phenyl-indanes and salts thereof with activity at dopamine receptors D 1 and D 2 as well as the 5HT 2 receptors in the central nervous system, to medicaments comprising such compounds as active ingredients, to the use of such compounds in the treatment of diseases in the central nervous system, and to methods of treatment comprising administration of such compounds.

  本发明涉及氘代1-哌嗪基-3-苯基茚烷及其盐，具有在中枢神经系统中对多巴胺受体D1和D2以及5HT2受体的活性，涉及包含这些化合物作为活性成分的药物、将这些化合物用于治疗中枢神经系统疾病的用途，以及包括给予这些化合物的治疗方法。
• Tartrate and Malate Salts of Trans-1-((1R,3S)-6-Chloro-3-Phenylindan-1-Yl)-3,3-Dimethylpiperazine
  申请人：Nielsen Ole

  公开号：US20080269248A1

  公开（公告）日：2008-10-30

  A tartrate and malate salt of trans-1-(6-chloro-3-phenylindan-1-yl)-3,3-dimethylpiperazine, in particular for medical use, pharmaceutical formulations thereof, including for treatment of schizophrenia or other diseases involving psychotic symptoms.

  一种酒石酸盐和苹果酸盐的trans-1-(6-氯-3-苯基茚-1-基)-3,3-二甲基哌嗪，特别用于医疗用途，包括用于治疗精神分裂症或其他涉及精神症状的疾病的制药配方。
• Process for Making Trans-1-((1R,3S)-6-Chloro-3-Phenylindan-1-Yl)-3,3-Dimethylpiperazine
  申请人：Dahl Allan Carsten

  公开号：US20080153847A1

  公开（公告）日：2008-06-26

  Described is a method for making the trans-1-((1R,3S)-6-chloro-3-phenylin-dan-1-yl)-3,3-dimethylpiperazine (formula I) and salts thereof and a similar method for making 4-((1R,3S)-6-chloro-3-phenylin-dan-1-yl)-1,2,2-trimethylpiperazine (formula IX) and salts thereof, which method comprises conversion of a compound of formula IVa to the compound of formula I or the compound of formula IX, respectively.

  本发明涉及一种制备trans-1-((1R,3S)-6-氯-3-苯基印丹-1-基)-3,3-二甲基哌嗪（式I）及其盐的方法，以及一种类似的制备4-((1R,3S)-6-氯-3-苯基印丹-1-基)-1,2,2-三甲基哌嗪（式IX）及其盐的方法，其中该方法包括将式IVa的化合物转化为式I的化合物或式IX的化合物。
• Crystalline Base of Trans-1-((1R,3S)-6-Chloro-3-Phenylindan-1-Yl)-3,3-Dimethylpiperazine
  申请人：Bang-Andersen Benny

  公开号：US20080153848A1

  公开（公告）日：2008-06-26

  Crystalline base of compound trans-1-((1R,3S)-6-chloro-3-phenylindan-1-yl)-3,3-dimethylpiperazine, processes for the preparation of purified free base or salts of this compound, pharmaceutical compositions comprising the base and medical use thereof, including for treatment of schizophrenia and other psychotic disorders.

  复合物trans-1-((1R,3S)-6-氯-3-苯基茚骈[1,2-b]吡嗪-1-基)-3,3-二甲基哌嗪的晶体基础，制备该化合物纯化自由碱或盐的工艺，包括该碱的制药组合物和医疗用途，包括治疗精神分裂症和其他精神疾病。