4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-4-oxobutan-1-one | 34104-51-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-4-oxobutan-1-one
• 英文别名: 4-(4-chloro-phenyl)-1-[4-(4-fluoro-phenyl)-4-oxo-butyryl]-piperidin-4-ol；1-[β-(p-fluorobenzoyl)propionyl]-4-(p-chlorophenyl)-4-hydroxypiperidine；1-(4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl)-4-(4-fluorophenyl)butane-1,4-dione；1-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-4-(4-fluorophenyl)butane-1,4-dione
• CAS: 34104-51-3
• 化学式: C₂₁H₂₁ClFNO₃
• 分子量: 389.854
• InChiKey: CPIWUAZRERXKBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-4-oxobutan-1-one 以 四氢呋喃 、 水 为溶剂， 生成 还原氟哌啶醇
  参考文献：
  名称：

  Phenylbutanol derivatives

  摘要：

  丁酮酚类衍生物具有出色的精神活性，其化学式表示为，##SPC1## 其中A代表单键或双键连接；R.sub.1代表氢原子或C.sub.1 - C.sub.4烷基团；R.sub.2（仅在A代表单键连接的情况下存在）代表氢原子，或羟基，C.sub.1 - C.sub.4烷基，或C.sub.1 - C.sub.4烷氧基团；R.sub.3代表氢原子，或哌啶基，吡咯啉基，吗啉基，呋喃基，噻吩基，C.sub.1 - C.sub.4烷基胺基，苄胺基，未取代或卤素取代的苯基等；X代表氢原子或卤素原子，或C.sub.1 - C.sub.4烷基，C.sub.1 - C.sub.4烷氧基，或三氟甲基基团，可通过将上述化学式的苯甲酰丙酰胺衍生物还原制备为苯基丁醇衍生物的方法得到，##SPC2## 其中A，R.sub.1，R.sub.2，R.sub.3和X的含义与上述定义相同，制备为苯基丁醇衍生物的化学式为，##SPC3##

  公开号：

  US03936468A1
• 作为产物：
  描述：

  3-(4-氟苯甲酰基)丙酸 在 草酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 46.0h， 生成 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-4-oxobutan-1-one
  参考文献：
  名称：

  Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2014.06.079

文献信息

• US3936468A
  申请人：——

  公开号：US3936468A

  公开（公告）日：1976-02-03
• 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.
• Phenylbutanol derivatives
  申请人：Sumitomo Chemical Company, Ltd.

  公开号：US03936468A1

  公开（公告）日：1976-02-03

  Butyrophenone derivatives having excellent psychotropic activity and represented by the formula, ##SPC1## Wherein A represents a single or double bond linkage; R.sub.1 represents a hydrogen atom or a C.sub.1 - C.sub.4 alkyl group; R.sub.2, which is present only in case A represents a single bond linkage, represents a hydrogen atom, or a hydroxyl, C.sub.1 - C.sub.4 alkyl, or C.sub.1 - C.sub.4 alkoxy group; R.sub.3 represents a hydrogen atom, or a piperidino, pyrrolidino, morpholino, furyl, thienyl, C.sub.1 - C.sub.4 alkylamino, benzylamino, unsubstituted or halogen-substituted phenyl group, etc.; and X represents a hydrogen or halogen atom, or a C.sub.1 - C.sub.4 alkyl, C.sub.1 - C.sub.4 alkoxy, or trifluoromethyl group, can be prepared by reducing a benzoylpropionamide derivative of the formula, ##SPC2## Wherein A, R.sub.1, R.sub.2, R.sub.3 and X have the same meanings as defined above, to a phenylbutanol derivative of the formula, ##SPC3##

  丁酮酚类衍生物具有出色的精神活性，其化学式表示为，##SPC1## 其中A代表单键或双键连接；R.sub.1代表氢原子或C.sub.1 - C.sub.4烷基团；R.sub.2（仅在A代表单键连接的情况下存在）代表氢原子，或羟基，C.sub.1 - C.sub.4烷基，或C.sub.1 - C.sub.4烷氧基团；R.sub.3代表氢原子，或哌啶基，吡咯啉基，吗啉基，呋喃基，噻吩基，C.sub.1 - C.sub.4烷基胺基，苄胺基，未取代或卤素取代的苯基等；X代表氢原子或卤素原子，或C.sub.1 - C.sub.4烷基，C.sub.1 - C.sub.4烷氧基，或三氟甲基基团，可通过将上述化学式的苯甲酰丙酰胺衍生物还原制备为苯基丁醇衍生物的方法得到，##SPC2## 其中A，R.sub.1，R.sub.2，R.sub.3和X的含义与上述定义相同，制备为苯基丁醇衍生物的化学式为，##SPC3##