2-[(3,4-dichlorophenyl)phenylmethoxy]ethyl bromide | 112952-32-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[(3,4-dichlorophenyl)phenylmethoxy]ethyl bromide
• 英文别名: 4-[2-Bromoethoxy(phenyl)methyl]-1,2-dichlorobenzene
• CAS: 112952-32-6
• 化学式: C₁₅H₁₃BrCl₂O
• 分子量: 360.078
• InChiKey: STYPCRFPORBXCW-UHFFFAOYSA-N

物化性质

• 沸点：
  414.0±40.0 °C(Predicted)
• 密度：
  1.463±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-[(3,4-dichlorophenyl)phenylmethoxy]ethyl bromide 在 lithium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 79.0h， 生成 3-piperidinecarboxylic acid, 1-[2-[(3,4-dichlorophenyl)phenylmethoxy]ethyl]-
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032
• 作为产物：
  描述：

  3,4-二氯二苯甲酮 在 sodium tetrahydroborate 、 硫酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 21.0h， 生成 2-[(3,4-dichlorophenyl)phenylmethoxy]ethyl bromide
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032

文献信息

• 1,4-Disubstituted piperazines having dopaminergic activity
  申请人：Richter Gedeon Vegyeszeti Gyar

  公开号：US04874765A1

  公开（公告）日：1989-10-17

  The invention relates to novel 1,4-disubstituted piperazine derivatives of the general formula (I), pharmaceutically acceptable acid addition and quaternary ammonium salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the general formula (I) ##STR1## R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are the same or different and stand for hydrogen or halogen or a trihalomethyl, lower alkyl, lower alkoxy, nitro, hydroxyl, aralkyloxy or an 1-(2-propenyl-4-piperazinyl) group; R.sub.5 stands for hydrogen or a C.sub.1-4 alkyl group; R.sub.6 represents a C.sub.3-6 alkyl, alkenyl, alkynyl group or a ##STR2## group, wherein R.sub.7 means a C.sub.2-5 alkyl, alkenyl or alkinyl group; and is 2 or 3, with the provisos that: R.sub.6 is different from isopropyl, n-butyl and isobutyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2; R.sub.6 is different from isopropyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2; or when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-methyl group and n is 2; and R.sub.6 is different from propionyl group when R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are hydrogen and n means 2. The compounds of the general formula (I) are therapeutically useful for the treatment of diseases arising from a hypofunction of the dopaminergic system.

  本发明涉及一种新颖的1,4-二取代哌嗪衍生物，其一般式为(I)，其中包括药学上可接受的酸加盐和季铵盐，以及含有它们的制药组合物和制备它们的方法。在一般式(I)中，R.sub.1、R.sub.2、R.sub.3和R.sub.4相同或不同，代表氢或卤素或三卤甲基、较低烷基、较低烷氧基、硝基、羟基、芳基烷氧基或1-(2-丙烯基-4-哌嗪基)基；R.sub.5代表氢或C.sub.1-4烷基；R.sub.6代表C.sub.3-6烷基、烯基、炔基或##STR2##基，其中R.sub.7表示C.sub.2-5烷基、烯基或炔基；n为2或3，具体规定如下：当R.sub.2、R.sub.3、R.sub.4和R.sub.5代表氢，R.sub.1表示2-氯且n为2时，R.sub.6与异丙基、正丁基和异丁基不同；当R.sub.2、R.sub.3、R.sub.4和R.sub.5代表氢，R.sub.1表示2-氯且n为2时，R.sub.6与异丙基不同；或当R.sub.2、R.sub.3、R.sub.4和R.sub.5代表氢，R.sub.1表示2-甲基且n为2时，R.sub.6与异丙基不同；当R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5均为氢，n为2时，R.sub.6与丙酰基不同。一般式(I)的化合物在治疗起因于多巴胺能系统低功能的疾病方面有治疗用途。
• US4874765A
  申请人：——

  公开号：US4874765A

  公开（公告）日：1989-10-17