(+/-)-4-chlorophenyl 4-(4-chlorophenyl)-4-hydroxy-1-methyl-3-piperidyl ketone | 21070-54-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (+/-)-4-chlorophenyl 4-(4-chlorophenyl)-4-hydroxy-1-methyl-3-piperidyl ketone
• 英文别名: (4-chloro-phenyl)-[4t-(4-chloro-phenyl)-4c-hydroxy-1-methyl-[3r]piperidyl]-ketone；(4-Chlor-phenyl)-[4t-(4-chlor-phenyl)-4c-hydroxy-1-methyl-[3r]piperidyl]-keton；(4-chlorophenyl)-[(3S,4R)-4-(4-chlorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone
• CAS: 21070-54-2
• 化学式: C₁₉H₁₉Cl₂NO₂
• 分子量: 364.271
• InChiKey: UFHWOVCVCKOHGI-MJGOQNOKSA-N

物化性质

• 熔点：
  156-159 °C
• 沸点：
  520.2±50.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,3'-methylimino bis(1-p-chlorophenyl-1-propanone) hydrochloride 在 sodium hydroxide 作用下， 生成 (+/-)-4-chlorophenyl 4-(4-chlorophenyl)-4-hydroxy-1-methyl-3-piperidyl ketone
  参考文献：
  名称：

  1,3,4-TRISUBSTITUTED PIPERIDINE DERIVATIVES FROM MANNICH BASES

  摘要：

  DOI：

  10.1021/jo01157a022

文献信息

• Molecular Modeling, Structure–Activity Relationships and Functional Antagonism Studies of 4-Hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-Methylphenyl Ketones as a Novel Class of Dopamine Transporter Inhibitors
  作者：Shaomeng Wang、Sukumar Sakamuri、Istvan J. Enyedy、Alan P. Kozikowski、Wahiduz A. Zaman、Kenneth M. Johnson

  DOI：10.1016/s0968-0896(01)00090-6

  日期：2001.7

  We previously disclosed the discovery of 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidul 4-methylphenyl ketone (3) as a novel class of dopamine transporter (DAT) inhibitors and showed that (+/-)-3 has a significant functional antagonism against cocaine in vitro. Our previous preliminary structure activity relationship study led to identification of a more potent DAT inhibitor [(+/-)-4] but this compound failed to show any significant functional antagonism To search for more potent analogues than 3 but still displaying significant functional antagonism, further SARs, molecular modeling studies and in vitro pharmacological evaluation of this novel class of DAT inhibitors were performed. Sixteen new analogues were synthesized in racemic form and evaluated as DAT inhibitors. It was found that seven new analogues are reasonably potent DAT inhibitors with K-i values of 0.041-0.30 and 0.052-0.16 muM in [H-3]mazindol binding and inhibition of DA reuptake. Chiral isomers of several potent DAT inhibitors were obtained through chiral HPLC separation and evaluated as inhibitors at all the three monoamine transporter sites. In general, the (-)-isomer is more active than the (+)-isomer in inhibition of DA reuptake and all the (-)-isomers are selective inhibitors at the DAT site. Evaluation of cocaine's effect on dopamine uptake in the presence and absence of (+)-3 and (-)-3 showed that (-)-3 is responsible For the functional antagonism obtained with the original lead (+/-)-3. Out of the new compounds synthesized, analogue (+/-)-20, which is 8- and 3-fold more potent than (+/-)-3 in binding and inhibition of DA reuptake. appeared to hare improved functional antagonism as compared to (+/-)-3. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 1,3,4-TRISUBSTITUTED PIPERIDINE DERIVATIVES FROM MANNICH BASES
  作者：JOHN T. PLATI、ROBERT A. SCHMIDT、WILHELM WENNER

  DOI：10.1021/jo01157a022

  日期：1949.9