4-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylic acid ethyl ester | 258500-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylic acid ethyl ester
• 英文别名: ethyl 4-(3,4-dichlorophenyl)-1-methyl-piperidine-4-carboxylate；3',4'-dichloromeperidine；ethyl 1-N-methyl-4-(3,4-dichlorophenyl)piperidine-4-carboxylate；ethyl 4-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylate
• CAS: 258500-91-3
• 化学式: C₁₅H₁₉Cl₂NO₂
• 分子量: 316.227
• InChiKey: CVNBITYLPWBHNX-UHFFFAOYSA-N

物化性质

• 沸点：
  385.4±42.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylic acid ethyl ester 在 1-氯乙基氯甲酸酯 、 碳酸氢钠 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 66.0h， 生成 4-(3,4-Dichloro-phenyl)-1-(3-methanesulfonyloxy-propyl)-piperidine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Structure–activity studies of 3′-4′-dichloro-meperidine analogues at dopamine and serotonin transporters

  摘要：

  The structure-activity relationships of 3',4'-dichloro-meperidine were investigated at dopamine (DAT) and serotonin transporters (SERT). Large ester substituents and lipophilic groups at the 4-position favored molecular recognition at the SERT. The benzyl ester of 3',4'-dichloro-meperidine exhibited high potency and high selectivity for the SERT (DAT/SERT = 760). Chemical modification of the ester group and N-substitution generally led to compounds with decreased DAT affinity. Only small esters and alkyl groups were tolerated at the 4-position of the meperidine ring system by the DAT. Overall, the meperidine analogues were generally more selective for the SERT than for the DAT. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.025
• 作为产物：
  描述：

  4-(3,4-二氯苯基)-1-甲基哌啶-4-甲腈 在 硫酸 作用下， 生成 4-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  哌替啶新型类似物的合成，多巴胺和5-羟色胺转运蛋白结合亲和力。

  摘要：

  合成了一系列哌啶类似物，并确定了与多巴胺和5-羟色胺转运蛋白的结合亲和力。苯环上的取代基极大地影响了这些化合物对转运蛋白结合位点的效力和选择性。通常，哌替啶（3）及其类似物对5-羟色胺转运蛋白结合位点的选择性更高，酯9比相应的腈8更有效。3,4-二氯衍生物9e是多巴胺转运蛋白系列中最有效的配体结合位点，而2-萘基衍生物9g表现出最强的结合亲和力，对5-羟色胺转运蛋白结合位点具有高度选择性。

  DOI：

  10.1016/s0960-894x(99)00606-x

文献信息

• [EN] NAPHTHYL ETHER COMPOUNDS AND THEIR USE<br/>[FR] COMPOSES DE NAPHTYL ETHER ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2004022539A1

  公开（公告）日：2004-03-18

  Compounds having the following structure wherein R1, R2, R3, R4, R5, R6, R7 m and n are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

  具有以下结构的化合物，其中R1、R2、R3、R4、R5、R6、R7、m和n如规范中定义，其体内可水解的前体，其药用盐，以及在治疗中的使用、制药组合物和使用相同的治疗方法。
• Synthesis, dopamine and serotonin transporter binding affinities of novel analogues of meperidine
  作者：Stacey A. Lomenzo、Sari Izenwasser、Robert M. Gerdes、Jonathan L. Katz、Theresa Kopajtic、Mark L. Trudell

  DOI：10.1016/s0960-894x(99)00606-x

  日期：1999.12

  of meperidine analogues was synthesized and the binding affinities for the dopamine and serotonin transporters were determined. The substituents on the phenyl ring greatly influenced the potency and selectivity of these compounds for the transporter binding sites. In general, meperidine (3) and its analogues were more selective for serotonin transporter binding sites and the esters 9 were more potent

  合成了一系列哌啶类似物，并确定了与多巴胺和5-羟色胺转运蛋白的结合亲和力。苯环上的取代基极大地影响了这些化合物对转运蛋白结合位点的效力和选择性。通常，哌替啶（3）及其类似物对5-羟色胺转运蛋白结合位点的选择性更高，酯9比相应的腈8更有效。3,4-二氯衍生物9e是多巴胺转运蛋白系列中最有效的配体结合位点，而2-萘基衍生物9g表现出最强的结合亲和力，对5-羟色胺转运蛋白结合位点具有高度选择性。
• Naphthyl ether compounds and their use
  申请人：Bernstein Peter

  公开号：US20050245572A1

  公开（公告）日：2005-11-03

  Compounds having the following structure wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 m and n are as defined in the specification, in vivo-hydrolysable precursors thereof, pharmaceutically-acceptable salts thereof, the use in therapy and pharmaceutical compositions and methods of treatment using the same.

  具有以下结构的化合物，其中R1、R2、R3、R4、R5、R6、R7m和n如规范中所定义，其体内可水解的前体物，其药学上可接受的盐，其在治疗中的应用以及使用其进行治疗的制药组合物和方法。
• Synthesis and structure–activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands
  作者：Xiaobo Gu、Sari Izenwasser、Dean Wade、Amy Housman、Gerard Gulasey、Jill B. Rhoden、Christopher D. Savoie、David L. Mobley、Stacey A. Lomenzo、Mark L. Trudell

  DOI：10.1016/j.bmc.2010.09.060

  日期：2010.12

  A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (K-i values <2 nM) and high SERT selectivity (DAT/SERT > 1500 and NET/SERT > 1500). (C) 2010 Elsevier Ltd. All rights reserved.
• NAPHTHYL ETHER COMPOUNDS AND THEIR USE
  申请人：AstraZeneca AB

  公开号：EP1546101A1

  公开（公告）日：2005-06-29