4-methyl-4-[3-(1-methylethoxy)phenyl]piperidine | 1585988-82-4

• 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-methyl-4-[3-(1-methylethoxy)phenyl]piperidine
• 英文别名: 4-Methyl-4-(3-propan-2-yloxyphenyl)piperidine
• CAS: 1585988-82-4
• 化学式: C₁₅H₂₃NO
• 分子量: 233.354
• InChiKey: VRMWTEJJTOZRHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methyl-4-[3-(1-methylethoxy)phenyl]piperidine 在 三氯化硼 、 sodium cyanoborohydride 作用下， 以 二氯甲烷 、 2,2,2-三氟乙醇 为溶剂， 反应 18.0h， 生成 3-(4-methyl-1-(3-phenylpropyl)piperidin-4-yl)phenol
  参考文献：
  名称：

  Effect of the 3- and 4-Methyl Groups on the Opioid Receptor Properties of N-Substituted trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines

  摘要：

  N-substituted trans-3,4-dimethy1-4-(3-hydroxyphenyOpiperidines (2a,b) are opioid receptor antagonists where the antagonist properties are not due to the type of N-substituent. In order to gain a better understanding of the contribution that the 3- and 4-methyl groups make to the pure antagonist properties of 2a,b, we synthesized analogues of 2a,b that lacked the 4-methyl (5a,b), 3-methyl (6a,b), and both the 3- and 4-methyl group (7a,b) and compared their opioid receptor properties. We found that (1) all N-methyl and N-phenylpropyl substituted compounds were nonselective opioid antagonists (2) all N-phenylpropyl analogues were more potent than their N-methyl counterparts, and (3) compounds 2a,b which have both a 3- and 4-methyl substituent, were more potent antagonists than analogues 5a,b, 6a,b, and 7a,b. We also found that the removal of 3-methyl substituent of N-methyl and N-phenylpropyl 3-methyl-4-(3-hydroxyphenyl)piperazines (8a,b) gives (4a,b), which are opioid antagonists.

  DOI：

  10.1021/jm500184j
• 作为产物：
  描述：

  在 甲醇 作用下， 反应 1.0h， 以677 mg的产率得到4-methyl-4-[3-(1-methylethoxy)phenyl]piperidine
  参考文献：
  名称：

  Effect of the 3- and 4-Methyl Groups on the Opioid Receptor Properties of N-Substituted trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines

  摘要：

  N-substituted trans-3,4-dimethy1-4-(3-hydroxyphenyOpiperidines (2a,b) are opioid receptor antagonists where the antagonist properties are not due to the type of N-substituent. In order to gain a better understanding of the contribution that the 3- and 4-methyl groups make to the pure antagonist properties of 2a,b, we synthesized analogues of 2a,b that lacked the 4-methyl (5a,b), 3-methyl (6a,b), and both the 3- and 4-methyl group (7a,b) and compared their opioid receptor properties. We found that (1) all N-methyl and N-phenylpropyl substituted compounds were nonselective opioid antagonists (2) all N-phenylpropyl analogues were more potent than their N-methyl counterparts, and (3) compounds 2a,b which have both a 3- and 4-methyl substituent, were more potent antagonists than analogues 5a,b, 6a,b, and 7a,b. We also found that the removal of 3-methyl substituent of N-methyl and N-phenylpropyl 3-methyl-4-(3-hydroxyphenyl)piperazines (8a,b) gives (4a,b), which are opioid antagonists.

  DOI：

  10.1021/jm500184j

文献信息

• [EN] KAPPA-OPIOID RECEPTOR SELECTIVE OPIOID RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS OPIOÏDES SÉLECTIFS DES RÉCEPTEURS OPIOÏDES KAPPA
  申请人：RES TRIANGLE INST

  公开号：WO2015109080A1

  公开（公告）日：2015-07-23

  Potent opioid receptor antagonists and there use as pharmacotherapies for treating depression, anxiety, schizophrenia, eating disorders, and addiction to cocaine, methamphetamine, nicotine, alcohol, and opiates are disclosed.

  强效阿片受体拮抗剂及其在治疗抑郁症、焦虑症、精神分裂症、进食障碍以及对可卡因、甲基苯丙胺、尼古丁、酒精和阿片类药物成瘾的药物治疗中的应用被披露。
• Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of the 3- and 4-methyl substituents
  作者：F. Ivy Carroll、Moses G. Gichinga、Chad M. Kormos、Rangan Maitra、Scott P. Runyon、James B. Thomas、S. Wayne Mascarella、Ann M. Decker、Hernán A. Navarro

  DOI：10.1016/j.bmc.2015.08.025

  日期：2015.10

  structure. In order to determine if the 3-methyl or 4-methyl groups were necessary in JDTic and JDTic analogs for antagonistic activity, compounds 4a–c, and 4d–f which have either the 3-methyl or both the 3- and 4-methyl groups removed, respectively, from JDTic and analogs were synthesized and evaluated for their in vitro opioid receptor antagonist activities using a [35S]GTPγS binding assay. Other ADME

  JDTic作为有效的选择性κ阿片受体拮抗剂的设计和发现，是使用N-取代的反式-3,4-二甲基-4-（3-羟苯基）哌啶药效基团作为前导结构的。为了确定在JDTic和JDTic类似物中拮抗活性是否需要3-甲基或4-甲基，化合物4a – c和4d – f具有3-甲基或同时具有3-和4-甲基分别从JDTic和类似物中除去的基团被合成，并使用[ 35]评估它们的体外阿片受体拮抗剂活性。S]GTPγS结合测定。还评估了所选化合物的其他ADME性质。这些研究表明，JDTic和类似物中存在的3-甲基或3,4-二甲基均不需要产生有效的选择性κ阿片受体拮抗剂。