4-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl]-1-(4-fluorophenyl)-1-butanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl]-1-(4-fluorophenyl)-1-butanone
• 英文别名: 4-[4-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one; hydrochloride；4-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-one
• 化学式: C₂₂H₂₅FN₂O₃
• 分子量: 384.451
• InChiKey: QHORYEWITOZOQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-4'-氟苯丁酮 、 1-(2,3-二氢-1,4-苯并二烷-5-基)哌嗪盐酸盐 在 三乙胺 作用下， 反应 18.0h， 生成 4-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl]-1-(4-fluorophenyl)-1-butanone
  参考文献：
  名称：

  Structure-Affinity Relationship Studies on 5-HT1A receptor Ligands. 2. Heterobicyclic Phenylpiperazines with N4-Aralkyl Substituents

  摘要：

  Structure-affinity relationship (SAR) studies for the 5HT(1A) receptor site are presented for two series of heterobicyclic phenylpiperazines with N4-aralkyl substituents: 4-aralkyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3) and 1-(benzo[b]furan-7-yl)piperazine (4). Their affinities far 5-HT1A receptors range from 0.15 to 28 nM and thus emphasize the importance of N4-substitution. By combining the SAR of these N4-aralkyl series with the recently published(11) SAR of the N4-alkyl-substituted phenylpiperazines, the nature of the interaction of the N4-substituted phenylpiperazines and the 5-HT1A receptor was further examined using comparative molecular field analysis (CoMFA). To discriminate between two postulated hypotheses, CoMFA models were built and validated utilizing cross-validation, bootstrapping, and randomizing techniques. The model based on a N4-substituent alignment in which all N4-substituents are equally oriented in space was selected for further evaluation. According to the CoMFA/PLS analysis, the steric and electrostatic field properties contribute in a 98:2 ratio to the affinity found for the 5HT(1A) receptor. Increasing steric bulk was found to be positively as well as negatively related to affinity depending on the distance of the bulk's center from the N4-nitrogen. The location of these steric CoMFA contour levels are well defined in space when the defined alignment rules are followed. Because CoMFA does not take hydrogen bonding into account, this could indicate that the contribution of the amide function (its ability to interact through hydrogen bonding), as present in the N4-substituents, to affinity is of minor importance.

  DOI：

  10.1021/jm00043a015

文献信息

• Structure-Affinity Relationship Studies on 5-HT1A receptor Ligands. 2. Heterobicyclic Phenylpiperazines with N4-Aralkyl Substituents
  作者：Bart J. van Steen、Ineke van Wijngaarden、Martin Th. M. Tulp、Willem Soudijn

  DOI：10.1021/jm00043a015

  日期：1994.8

  Structure-affinity relationship (SAR) studies for the 5HT(1A) receptor site are presented for two series of heterobicyclic phenylpiperazines with N4-aralkyl substituents: 4-aralkyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3) and 1-(benzo[b]furan-7-yl)piperazine (4). Their affinities far 5-HT1A receptors range from 0.15 to 28 nM and thus emphasize the importance of N4-substitution. By combining the SAR of these N4-aralkyl series with the recently published(11) SAR of the N4-alkyl-substituted phenylpiperazines, the nature of the interaction of the N4-substituted phenylpiperazines and the 5-HT1A receptor was further examined using comparative molecular field analysis (CoMFA). To discriminate between two postulated hypotheses, CoMFA models were built and validated utilizing cross-validation, bootstrapping, and randomizing techniques. The model based on a N4-substituent alignment in which all N4-substituents are equally oriented in space was selected for further evaluation. According to the CoMFA/PLS analysis, the steric and electrostatic field properties contribute in a 98:2 ratio to the affinity found for the 5HT(1A) receptor. Increasing steric bulk was found to be positively as well as negatively related to affinity depending on the distance of the bulk's center from the N4-nitrogen. The location of these steric CoMFA contour levels are well defined in space when the defined alignment rules are followed. Because CoMFA does not take hydrogen bonding into account, this could indicate that the contribution of the amide function (its ability to interact through hydrogen bonding), as present in the N4-substituents, to affinity is of minor importance.