3,5-二氯-N-[[1-(2-氟乙基)吡咯烷-2-基]甲基]-2-羟基-6-甲氧基苯甲酰胺 | 124840-52-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3,5-二氯-N-[[1-(2-氟乙基)吡咯烷-2-基]甲基]-2-羟基-6-甲氧基苯甲酰胺
• 英文名称: (S)-2-<(3,5-dichloro-6-methoxy-2-hydroxybenzamido)methyl>-1-(2-fluoroethyl)pyrrolidine
• 英文别名: Fluororaclopride；3,5-dichloro-N-[[(2S)-1-(2-fluoroethyl)pyrrolidin-2-yl]methyl]-2-hydroxy-6-methoxybenzamide
• CAS: 124840-52-4
• 化学式: C₁₅H₁₉Cl₂FN₂O₃
• 分子量: 365.232
• InChiKey: SUMSSRZHRHBCGI-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-2-<(3,5-dichloro-2,6-dimethoxybenzamido)methyl>-1-(2-fluoroethyl)pyrrolidine hydrochloride 在 盐酸 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 3,5-二氯-N-[[1-(2-氟乙基)吡咯烷-2-基]甲基]-2-羟基-6-甲氧基苯甲酰胺
  参考文献：
  名称：

  N-Fluoroalkylated and N-alkylated analogs of the dopaminergic D-2 receptor antagonist raclopride

  摘要：

  A series of raclopride [(S)-2-[(3,5-dichloro-6-methoxy-2- hydroxybenzamido)methyl]-1-ethylpyrrolidine] derivatives bearing pyrrolidino N-fluoroalkyl or -alkyl substituents were synthesized and evaluated as potential dopaminergic receptor-based positron tomography radiopharmaceuticals. Radiosynthetic procedures for producing the corresponding N-[18F]fluoroalkylated analogues of raclopride from 18F- (beta+, t1/2 = 110 min) in high specific activity were also developed. In vitro binding assays using competitive displacement of [3H]spiperone from primate caudate tissue indicated that the N-alkylated analogues of raclopride had Ki values of 5-40 nM, whereas the corresponding values for analogous N-fluoroalkylated derivatives ranged from 90-160 nM. The relatively low D-2 binding affinity of these fluorinated salicylamides was corroborated by in vivo tissue biodistribution results in rodents. On the basis of structure-binding correlations, the impact of intramolecular hydrogen bonding, ligand basicity, and steric bulk on the affinity of the benzamides for D-2 receptor binding are discussed. Strategies are presented for the development of alternative fluorinated salicylamides that are both receptor active and metabolically stable.

  DOI：

  10.1021/jm00171a017

文献信息

• N-Fluoroalkylated and N-alkylated analogs of the dopaminergic D-2 receptor antagonist raclopride
  作者：G. S. Lannoye、Stephen M. Moerlein、D. Parkinson、M. J. Welch

  DOI：10.1021/jm00171a017

  日期：1990.9

  A series of raclopride [(S)-2-[(3,5-dichloro-6-methoxy-2- hydroxybenzamido)methyl]-1-ethylpyrrolidine] derivatives bearing pyrrolidino N-fluoroalkyl or -alkyl substituents were synthesized and evaluated as potential dopaminergic receptor-based positron tomography radiopharmaceuticals. Radiosynthetic procedures for producing the corresponding N-[18F]fluoroalkylated analogues of raclopride from 18F- (beta+, t1/2 = 110 min) in high specific activity were also developed. In vitro binding assays using competitive displacement of [3H]spiperone from primate caudate tissue indicated that the N-alkylated analogues of raclopride had Ki values of 5-40 nM, whereas the corresponding values for analogous N-fluoroalkylated derivatives ranged from 90-160 nM. The relatively low D-2 binding affinity of these fluorinated salicylamides was corroborated by in vivo tissue biodistribution results in rodents. On the basis of structure-binding correlations, the impact of intramolecular hydrogen bonding, ligand basicity, and steric bulk on the affinity of the benzamides for D-2 receptor binding are discussed. Strategies are presented for the development of alternative fluorinated salicylamides that are both receptor active and metabolically stable.