Methyl 3-amino-5-chloro-1-cyano-1-phenylindene-2-carboxylate | 116617-20-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: Methyl 3-amino-5-chloro-1-cyano-1-phenylindene-2-carboxylate
• CAS: 116617-20-0
• 化学式: C₁₈H₁₃ClN₂O₂
• 分子量: 324.766
• InChiKey: YWJHZAIUJRKGBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 3-amino-5-chloro-1-cyano-1-phenylindene-2-carboxylate 在 N-甲基吡咯烷酮 、 sodium tetrahydroborate 、 甲酸 、 氯化亚砜 、 氢气 、 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：

  2,5-二氯苯甲腈 、 苯乙腈 、 氯乙酸甲酯 在 potassium tert-butylate 作用下， 生成 Methyl 3-amino-5-chloro-1-cyano-1-phenylindene-2-carboxylate
  参考文献：
  名称：

  Application of (2-cyanoaryl)arylacetonitriles in cyclization and annulation reactions. Preparation of 3-arylindans, 4-aryl-3,4-dihydronaphthalenes, 4-arylisoquinolines, 1-aminonaphthalenes, and heterocyclic analogues

  摘要：

  DOI：

  10.1021/jo00303a012

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。
• 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。
• 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：US20100069676A1

  公开（公告）日：2010-03-18

  Described is a method for making the trans-1-((1R,3S)-6-chloro-3-phenylindan-1-yl)-3,3-dimethylpiperazine (formula I) and salts thereof and a similar method for making 4-((1R,3S)-6-chloro-3-phenylindan-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.

  本文描述了一种制备trans-1-((1R,3S)-6-氯-3-苯基茚环-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-苯基茚环-1-基)-1,2,2-三甲基哌嗪（式IX）及其盐的方法，该方法包括将化合物IVa转化为式I或式IX的化合物。
• PROCESSES FOR 4-((1R,3S)-6-CHLORO-3-PHENYLINDAN-1-YL)-1,2,2-TRIMETHYLPIPERAZINE OR A SALT THEREOF
  申请人：Lopez de Diego Heidi

  公开号：US20100324291A1

  公开（公告）日：2010-12-23

  Methods for the preparation of 4-((1R,3S)-6-Chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and salts thereof are described.

  本文描述了制备4-((1R,3S)-6-氯-3-苯基茚烷-1-基)-1,2,2-三甲基哌嗪及其盐的方法。
• WO2006/86984
  申请人：——

  公开号：——

  公开（公告）日：——