1-[4-(4-Fluorophenyl)-4-oxobutyl]-4-benzamidopiperidine | 36793-62-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-(4-Fluorophenyl)-4-oxobutyl]-4-benzamidopiperidine
• 英文别名: N-[1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]benzamide
• CAS: 36793-62-1
• 化学式: C₂₂H₂₅FN₂O₂
• 分子量: 368.451
• InChiKey: NOMPHPRJDQKAFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-(4-Fluorophenyl)-4-oxobutyl]-4-benzamidopiperidine 在 sodium borohydrid 作用下， 以 甲醇 、 sodium hydroxide 为溶剂， 生成 1-[4-(p-Fluorophenyl)-4-hydroxybutyl]-4-benzamidopiperidine
  参考文献：
  名称：

  Pharmaceutical compositions and methods of treating hypertension

  摘要：

  本发明描述了含有杂环化合物组的药物组合物及其在治疗心血管系统疾病和/或治疗浅表和深层过敏现象中的应用。这些组合物和/或方法中使用的化合物是哌啶化合物，通过氮原子与取代或未取代的环烷基、芳基或杂环基团相连，中间通过一个选自低级烷叉基、单酮低级烷叉基或羟基低级烷叉基的基团，或一个二价基团，其公式为--NH.CO.(CH.sub.2).sub.n --，其中n为1、2或3，##STR1##或--O-(低级烷叉基)--。哌啶环进一步被酰胺基残基取代。

  公开号：

  US04029801A1
• 作为产物：
  描述：

  4-苯氨基-哌啶 、 4-氯-4'-氟苯丁酮 在 potassium carbonate 、 sodium iodide 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以37%的产率得到1-[4-(4-Fluorophenyl)-4-oxobutyl]-4-benzamidopiperidine
  参考文献：
  名称：

  Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist

  摘要：

  DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a ''5-HT2-selective'' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4-fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one(26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.

  DOI：

  10.1021/jm00069a010

文献信息

• Heterocyclic compounds
  申请人：John Wyeth & Brother Limited

  公开号：US03992389A1

  公开（公告）日：1976-11-16

  A group of heterocyclic compounds useful in the treatment of disorders and diseases of the cardiovascular system and/or in the treatment of superficial and deep allergic phenomena is described. These compounds are piperidine compounds linked by the nitrogen atom to a substituted or unsubstituted phenyl radical through the intermediary of a group selected from a lower-alkylene radical, a mono-keto lower alkylene radical or a hydroxy-lower-alkylene radical, or a bivalent radical of the formula ##EQU1## or --O--(lower-alkylene)-. The piperidine rings are further substituted by a benzamido, substituted benzamido or cyclohexylcarboxamido residue.

  描述了一组在治疗心血管系统疾病和过敏现象方面有用的杂环化合物。这些化合物是通过氮原子与一个取代或未取代苯基通过选择自低烷基基团、单酮基低烷基基团或羟基-低烷基基团、或者公式##EQU1##的双价基团或--O--(低烷基)-连接的哌啶化合物。哌啶环进一步取代为苯甲酰胺基、取代苯甲酰胺基或环己基羧酰胺基残基。
• Piperidino compounds
  申请人：John Wyeth & Brother Limited

  公开号：US04046767A1

  公开（公告）日：1977-09-06

  Novel piperidine compounds and their use in treatment of disorders and diseases of the cardiovascular system and/or in the treatment of superficial and deep allergic phenomena is described. These compounds are piperidine compounds linked by the nitrogen atom to cycloalkyl or a substituted or unsubstituted phenyl radical through the intermediary of a lower-alkylene radical. The piperidine ring is further substituted by an acylamino residue.

  本发明描述了新型哌啶类化合物及其在治疗心血管系统疾病和/或治疗浅表和深部过敏现象中的应用。这些化合物是哌啶类化合物，通过氮原子与环烷基或取代或未取代的苯基通过较低烷基的中介连接。哌啶环进一步被酰胺基残基取代。
• Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist
  作者：Abd M. Ismaiel、Joseph De Los Angeles、Milt Teitler、Stacy Ingher、Richard A. Glennon

  DOI：10.1021/jm00069a010

  日期：1993.8

  DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a ''5-HT2-selective'' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4-fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one(26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.
• US4069331A
  申请人：——

  公开号：US4069331A

  公开（公告）日：1978-01-17
• Pharmaceutical compositions and methods of treating hypertension
  申请人：John Wyeth & Brother Limited

  公开号：US04029801A1

  公开（公告）日：1977-06-14

  Pharmaceutical compositions containing a group of heterocyclic compounds and their use in treatment of disorders and diseases of the cardiovascular system and/or in the treatment of superficial and deep allergic phenomena is described. These compounds used in the composition and/or methods are piperidine compounds linked by the nitrogen atom to a substituted or unsubstituted cycloalkyl, aryl or heterocyclic radical through the intermediary of a group selected from a lower-alkylene radical, a monoketo lower-alkylene radical or a hydroxy-lower-alkylene radical, or a bivalent radical of the formula --NH.CO.(CH.sub.2).sub.n -- where n is 1, 2 or 3, ##STR1## or --0-(lower-alkylene)--. The piperidine ring is further substituted by an acylamino residue.

  本发明描述了含有杂环化合物组的药物组合物及其在治疗心血管系统疾病和/或治疗浅表和深层过敏现象中的应用。这些组合物和/或方法中使用的化合物是哌啶化合物，通过氮原子与取代或未取代的环烷基、芳基或杂环基团相连，中间通过一个选自低级烷叉基、单酮低级烷叉基或羟基低级烷叉基的基团，或一个二价基团，其公式为--NH.CO.(CH.sub.2).sub.n --，其中n为1、2或3，##STR1##或--O-(低级烷叉基)--。哌啶环进一步被酰胺基残基取代。