N,N-dimethyl-2,2-diphenyl-4-[4-[2-(2-hydroxyethoxy)phenyl]piperazin-1-yl]butanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N-dimethyl-2,2-diphenyl-4-[4-[2-(2-hydroxyethoxy)phenyl]piperazin-1-yl]butanamide
• 英文别名: 4-[4-[2-(2-hydroxyethoxy)phenyl]piperazin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide
• 化学式: C₃₀H₃₇N₃O₃
• 分子量: 487.642
• InChiKey: ARNKVVLIOGKDQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(2-羟基苯基)哌嗪 在 sodium hydroxide 、 sodium carbonate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 N,N-dimethyl-2,2-diphenyl-4-[4-[2-(2-hydroxyethoxy)phenyl]piperazin-1-yl]butanamide
  参考文献：
  名称：

  New .MU.-Opioid Receptor Agonists with Phenoxyacetic Acid Moiety.

  摘要：

  合成并评估了含有 4-羟基哌啶、哌啶和哌嗪分子的新型μ-阿片受体（MOR）激动剂，以寻找一种外周阿片类镇痛药。在合成的化合物中，[2-[1-[3-（N,N-二甲基氨基甲酰基）-3,3-二苯基丙基]-4-羟基哌啶-4-基]苯氧基]乙酸（8：在离体豚鼠回肠制剂中，具有苯氧乙酸和 4-羟基哌啶分子的 SS620 对 MOR 的激动效力最高，与同类型的 δ- 和 κ- 阿片受体（DOR 和 KOR）相比，它对中国仓鼠卵巢（CHO）-K1 细胞中表达的人类 MOR 也具有选择性。）此外，化合物 8 显示出的 MOR 激动剂活性是洛哌丁胺的 10 倍。此外，化合物 8 在大鼠体内筛选中显示出外周镇痛活性。

  DOI：

  10.1248/cpb.50.292

文献信息

• 2,2-Diphenylbutanamide derivatives and medicines containing the same
  申请人：——

  公开号：US20040034104A1

  公开（公告）日：2004-02-19

  2,2-Diphenylbutanamide derivatives represented by the following formula (1): 1 [wherein A represents —(CH 2 ) n — (n is 1 or 2) or a methine (CH) group; when A is —CH 2 —, B represents a methine group or a nitrogen atom, with A and B forming a single bond; when A is —(CH 2 ) 2 —, B represents a nitrogen atom, with A and B forming a single bond; when A is a methine group, B represents a quaternary carbon atom, with A and B forming a double bond; each of R 1 and R 2 , which are identical to or different from each other, represents a hydrogen atom, a lower alkyl group, or a cycloalkyl group, or R 1 and R 2 may form a heterocyclic ring together with the adjacent nitrogen atom; and Ar represents an optionally substituted phenyl group, bicyclic aromatic ring, monocyclic heterocyclic ring, bicyclic heterocyclic ring, or fluorene group]; or salts of the derivatives. The derivatives or salts thereof exhibit excellent &mgr;-opioid agonist activity and analgesic activity against neuropathic pain, and are useful as medicines such as peripheral analgesic drugs and neuropathic pain relieving drugs.

  以下式子（1）所表示的2,2-二苯基丁酰胺衍生物： 1[其中，A代表—（CH2）n—（n为1或2）或甲基（CH）基团；当A为—CH2—时，B代表甲基基团或氮原子，A和B形成单键；当A为—（CH2）2—时，B代表氮原子，A和B形成单键；当A为甲基基团时，B代表四价碳原子，A和B形成双键；R1和R2各自表示氢原子、低碳基或环烷基，或者R1和R2与相邻氮原子一起形成杂环；Ar表示可选取代的苯基、双环芳香环、单环杂环环、双环杂环环或芴基；以及其衍生物的盐。] 这些衍生物或其盐表现出优异的μ-阿片受体激动剂活性和对神经病理性疼痛的镇痛活性，可用作外周镇痛药和神经病理性疼痛缓解药等药物。
• 2,2-DIPHENYLBUTANAMIDE DERIVATIVES AND MEDICINES CONTAINING THE SAME
  申请人：SSP Co., Ltd.

  公开号：EP1325912A1

  公开（公告）日：2003-07-09

  2,2-Diphenylbutanamide derivatives represented by the following formula (1): [wherein A represents -(CH2)n- (n is 1 or 2) or a methine (CH) group; when A is -CH2-, B represents a methine group or a nitrogen atom, with A and B forming a single bond; when A is -(CH2)2-, B represents a nitrogen atom, with A and B forming a single bond; when A is a methine group, B represents a quaternary carbon atom, with A and B forming a double bond; each of R1 and R2, which are identical to or different from each other, represents a hydrogen atom, a lower alkyl group, or a cycloalkyl group, or R1 and R2 may form a heterocyclic ring together with the adjacent nitrogen atom; and Ar represents an optionally substituted phenyl group, bicyclic aromatic ring, monocyclic heterocyclic ring, bicyclic heterocyclic ring, or fluorene group]; or salts of the derivatives. The derivatives or salts thereof exhibit excellent µ-opioid agonist activity and analgesic activity against neuropathic pain, and are useful as medicines such as peripheral analgesic drugs and neuropathic pain relieving drugs.

  下式(1)代表的 2,2-二苯基丁酰胺衍生物： [其中 A 代表-(CH2)n-(n 为 1 或 2)或甲烷(CH)基；当 A 为-CH2-时，B 代表甲烷基或氮原子，A 和 B 形成单键；当 A 为-(CH2)2-时，B 代表氮原子，A 和 B 形成单键；当 A 为甲烷基时，B 代表季碳原子，A 和 B 形成双键；R1和R2（它们彼此相同或不同）各自代表氢原子、低级烷基或环烷基，或 R1和R2可与相邻的氮原子一起形成杂环；Ar代表任选取代的苯基、双环芳环、单环杂环、双环杂环或芴基】；或衍生物的盐。 这些衍生物或其盐具有优异的μ-类阿片激动剂活性和针对神经病理性疼痛的镇痛活性，可用作外周镇痛药物和神经病理性疼痛缓解药物。
• EP1325912
  申请人：——

  公开号：——

  公开（公告）日：——
• New .MU.-Opioid Receptor Agonists with Phenoxyacetic Acid Moiety.
  作者：Susumu Sato、Teruo Komoto、Yoshihiko Kanamaru、Noriyuki Kawamoto、Tomomi Okada、Terumitsu Kaiho、Kinichi Mogi、Shinichi Morimoto、Norimitsu Umehara、Tadayuki Koda、Akira Miyashita、Takao Sakamoto、Yasuhiro Niino、Tetsuo Oka

  DOI：10.1248/cpb.50.292

  日期：——

  New μ-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, [2-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of δ- and κ-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.

  合成并评估了含有 4-羟基哌啶、哌啶和哌嗪分子的新型μ-阿片受体（MOR）激动剂，以寻找一种外周阿片类镇痛药。在合成的化合物中，[2-[1-[3-（N,N-二甲基氨基甲酰基）-3,3-二苯基丙基]-4-羟基哌啶-4-基]苯氧基]乙酸（8：在离体豚鼠回肠制剂中，具有苯氧乙酸和 4-羟基哌啶分子的 SS620 对 MOR 的激动效力最高，与同类型的 δ- 和 κ- 阿片受体（DOR 和 KOR）相比，它对中国仓鼠卵巢（CHO）-K1 细胞中表达的人类 MOR 也具有选择性。）此外，化合物 8 显示出的 MOR 激动剂活性是洛哌丁胺的 10 倍。此外，化合物 8 在大鼠体内筛选中显示出外周镇痛活性。