4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl acetate | 115250-18-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl acetate
• 英文别名: haloperidol acetate；4-[4-(p-chlorophenyl)-4-acetoxypiperidinyl]-4'-fluorobutyrophenone；4-(4-Acetoxy-4-(4-chlorophenyl)-1-piperidinyl)-1-(4-fluorophenyl)-1-butanone；[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] acetate
• CAS: 115250-18-5
• 化学式: C₂₃H₂₅ClFNO₃
• 分子量: 417.908
• InChiKey: DQMKFVKNNDMGTA-UHFFFAOYSA-N

物化性质

• 熔点：
  107-109 °C(Solv: methanol (67-56-1); ethyl ether (60-29-7))
• 沸点：
  532.1±50.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  氟哌啶醇 、 乙酸酐 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以29%的产率得到4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl acetate
  参考文献：
  名称：

  人羧酸酯酶代谢激活的氟哌啶醇酯前药的合成与评价

  摘要：

  合成了两种对羟基或羰基进行了化学修饰的氟哌啶醇前药，并在人肝微粒体（HLM）溶液，人小肠微粒体（HIM）溶液和人重组羧酸酯酶（hCES）的溶液。HLM溶液中的醇酯前药的代谢活化率与hCES2溶液中的相似，而氟哌啶醇戊酸酯和氟哌啶醇己酸酯在合成的醇酯前药中具有较高的代谢活化率。此外，乙酸氟哌啶醇和氟哌啶醇2-甲基丁酸酯的水解速度与氟哌啶醇癸酸酯一样慢。结果表明具有小链或支链的氟哌啶醇前药可用作持续释放的前药。

  DOI：

  10.1016/j.ejps.2019.03.009

文献信息

• Acetic acid ester of haloperidol
  申请人：H. Lundbeck A/S

  公开号：US04855307A1

  公开（公告）日：1989-08-08

  The present invention relates to the novel acetic acid ester of 4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4-fluorophenyl)-1-butano ne, as well as pharmaceutically acceptable acid addition salts thereof, a method of preparation, pharmaceutical compositions and a method of treating psychoses by administering said ester to an animal or human body.

  本发明涉及一种新型的乙酸酯，其为4-(4-(4-氯苯基)-4-羟基-1-哌啶基)-1-(4-氟苯基)-1-丁酮的乙酸酯，以及其药学上可接受的酸盐加成物、制备方法、药物组合物和将该酯物用于治疗动物或人体的精神病的方法。
• The acetic acid ester of haloperidol and pharmaceutical compositions thereof
  申请人：H. LUNDBECK A/S

  公开号：EP0260070A1

  公开（公告）日：1988-03-16

  The novel acetic acid ester of 4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-­(4-fluorophenyl)-1-butanone (Haloperidol) as well as acid addition salts thereof are described, and a method of preparation of said compounds. Pharmaceutical compositions containing one of said compounds are described in form of injectable solutions in oils, e.g. sesame oil and light vegetable oil, which have advantages compared with known solutions of haloperidol.

  描述了 4-(4-(4-氯苯基)-4-羟基-1-哌啶基)-1-(4-氟苯基)-1-丁酮（氟哌啶醇）的新型乙酸酯及其酸加成盐，以及上述化合物的制备方法。 描述了含有上述化合物之一的药物组合物，其形式为油（如芝麻油和轻质植物油）中的可注射溶液，与已知的氟哌啶醇溶液相比具有优势。
• Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors
  作者：Ismail Salama、Stefan Löber、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.bmcl.2014.06.079

  日期：2014.8

  Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.
• US4855307A
  申请人：——

  公开号：US4855307A

  公开（公告）日：1989-08-08
• US5583000A
  申请人：——

  公开号：US5583000A

  公开（公告）日：1996-12-10