N-(3-(4-benzylpiperidin-1-yl)propyl)-2,2-diphenylacetamide

• 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: N-(3-(4-benzylpiperidin-1-yl)propyl)-2,2-diphenylacetamide
• 英文别名: N-[3-(4-Benzyl-piperidin-1-yl)-propyl]-2,2-diphenyl-acetamide；N-[3-(4-benzylpiperidin-1-yl)propyl]-2,2-diphenylacetamide
• 化学式: C₂₉H₃₄N₂O
• 分子量: 426.602
• InChiKey: DKXNWXXUHISEHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-苄基哌啶 在 镍 氨 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 N-(3-(4-benzylpiperidin-1-yl)propyl)-2,2-diphenylacetamide
  参考文献：
  名称：

  A Structure−Activity Relationship Study of Novel Phenylacetamides Which Are Sodium Channel Blockers

  摘要：

  A structure-activity relationship study of a series of novel Na+ channel blockers, structurally related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenylbenzeneacetamide (1, PD85639) is described. The diphenylacetic acid portion of the molecule was left unchanged throughout the study, while structural features in the amine portion and the amide alkyl linkage of the molecule were modified. The compounds were tested for inhibition of veratridine-stimulated Na+ influx in CHO cells expressing type IIA Na+ channels. Several derivatives show a trend toward more potent Na+ channel blockade activity with increasing lipophilicity of the amine portion of the molecule. The presence of a phenyl ring near the amine increases inhibitory potency. A three-carbon spacer between the amide and amine is optimal, and a secondary amide linkage is preferred.

  DOI：

  10.1021/jm950467y

文献信息

• Design, synthesis and in vitro activity of 1,4-disubstituted piperazines and piperidines as triple reuptake inhibitors
  作者：Suresh Paudel、Srijan Acharya、Goo Yoon、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2017.02.051

  日期：2017.4

  currently appear to be the potential target in the management of these disorders. In this study, homologation and bioisosterism techniques have been used in the designing of new 1,4-disubstituted piperazines and piperidines. These derivatives were synthesized and evaluated as potential triple reuptake inhibitors for studying the structure-activity relationships. The most advanced compound, 1-(4-(5-

  单胺转运蛋白调节着单胺神经递质的浓度，这对于重要的生理过程至关重要，其功能障碍会导致多种中枢神经系统疾病。目前，单胺转运蛋白似乎是这些疾病管理中的潜在靶标。在这项研究中，同源性和生物立体异构技术已被用于设计新的1,4-二取代哌嗪和哌啶。这些衍生物被合成并评估为潜在的三重再摄取抑制剂，用于研究结构-活性关系。最先进的化合物1-（4-（5-苯甲酰基-1H-四唑-1-基）丁基）-4-（3-苯丙基）哌嗪（2i）在体外测试中能够抑制单胺神经递质的再摄取（对于5-HT，IC50 = 158.7nM，对于NE，IC50 = 99nM，对于DA，IC50 = 97.5nM）。
• 신규한 1,4-치환된 피페라진 또는 피페리딘 화합물 및 이를 포함하는 약학적 조성물
  申请人：INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY 전남대학교산학협력단(220040365775) BRN ▼409-82-11942

  公开号：KR101819472B1

  公开（公告）日：2018-01-17

  본 발명은 하기 화학식 1의 화합물 또는 이의 약제학적으로 허용 가능한 염에 관한 것이다: [화학식 1] 상기 화학식 1에서, R 및 R는 서로 독립적으로 수소, 할로겐,탄소수 1 내지 4인 알킬기, 탄소수 1 내지 4인 알콕시기, 또는 트리플루오로메틸이고; R는 직접 결합, 탄소수 1 내지 4인 알킬기, 또는 탄소수 2 내지 4인 알케닐이고; R는 치환 또는 비치환된 탄소수 6 내지 10인 아릴기, 또는 치환 또는 비치환된 탄소수 6 내지 10인 헤테로아릴기이고, 상기 R의 치환된 아릴기 및 헤테로아릴기는 서로 독립적으로 할로겐, 탄소수 1 내지 4인 알킬기, 또는 탄소수 1 내지 4인 알콕시기로 치환된 것이고; X는 C 또는 N이고; Y는 O, CONH, NHCO 또는 이고; n은 0 내지 4의 정수인 것이다.

  该专利涉及化学式1中的化合物或其药理学上可接受的盐：[化学式1] 在上述化学式1中，R和R分别独立地表示氢，卤素，1至4个碳原子的烷基，1至4个碳原子的氧烷基，或三氟甲基；R直接连接，表示1至4个碳原子的烷基，或表示2至4个碳原子的烯基；R代表取代或未取代的含6至10个碳原子的芳基，或取代或未取代的含6至10个碳原子的杂环芳基，R的取代芳基和杂环芳基可以独立地被卤素，1至4个碳原子的烷基，或1至4个碳原子的氧烷基取代；X为C或N；Y为O，CONH，NHCO或；n为0到4之间的整数。
• Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors
  作者：Suresh Paudel、Yongkai Cao、Shuohan Guo、Byeongkwan An、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2015.08.022

  日期：2015.10

  A series of 4-benzylpiperidine carboxamides were designed and synthesized, and tested for their dual (serotonin and norepinephrine) reuptake inhibition. The synthesis of 4-benzylpiperidine carboxamides involved two main steps: amidation and substitution. Derivatives with 3 carbon linker displayed better activity than with 2 carbon linker. 4-Biphenyl- and 2-naphthyl-substituted derivatives 7e and 7j showed greater dual reuptake inhibition than standard drug venlafaxine HCl. (C) 2015 Elsevier Ltd. All rights reserved.
• A Structure−Activity Relationship Study of Novel Phenylacetamides Which Are Sodium Channel Blockers
  作者：Ioannis Roufos、Sheryl Hays、Roy D. Schwarz

  DOI：10.1021/jm950467y

  日期：1996.1.1

  A structure-activity relationship study of a series of novel Na+ channel blockers, structurally related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenylbenzeneacetamide (1, PD85639) is described. The diphenylacetic acid portion of the molecule was left unchanged throughout the study, while structural features in the amine portion and the amide alkyl linkage of the molecule were modified. The compounds were tested for inhibition of veratridine-stimulated Na+ influx in CHO cells expressing type IIA Na+ channels. Several derivatives show a trend toward more potent Na+ channel blockade activity with increasing lipophilicity of the amine portion of the molecule. The presence of a phenyl ring near the amine increases inhibitory potency. A three-carbon spacer between the amide and amine is optimal, and a secondary amide linkage is preferred.