1-(4,4-二苯基-3-丁烯)-3-哌啶羧酸盐酸盐 | 85375-15-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4,4-二苯基-3-丁烯)-3-哌啶羧酸盐酸盐
• 中文别名: 1-(4,4-二苯基-3-丁烯基)-3-哌啶盐酸盐；1-(4,4-二苯基-3-丁烯-1-基)-3-哌啶甲酸盐酸盐；1-（4,4-二苯基-3-丁烯基）-3-哌啶盐酸盐；1 - (4,4 - 二苯基-3 - 丁烯基)- 3 -哌啶盐酸盐
• 英文名称: SKF 89976A
• 英文别名: 1-(4,4-Diphenylbut-3-en-1-yl)piperidine-3-carboxylic acid hydrochloride；1-(4,4-diphenylbut-3-enyl)piperidine-3-carboxylic acid;hydrochloride
• CAS: 85375-15-1
• 化学式: C₂₂H₂₅NO₂*ClH
• 分子量: 371.907
• InChiKey: SNGGBKYQZVAQKA-UHFFFAOYSA-N

物化性质

• 溶解度：
  在DMSO中的溶解度为20 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  26
• 可旋转键数：
  6
• 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：
  2
• 氢受体数：
  3

安全信息

• WGK Germany：
  3
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313
• 危险性描述：
  H315,H319,H335

制备方法与用途

生物活性

SKF89976A 氢氯化物是一种选择性 GABA 转运蛋白 GAT-1 抑制剂，作用于 CHO 细胞中的 GAT-1、GAT-2 和 GAT-3，IC50 值分别为 0.28 μM、137.34 μM 和 202.8 μM。

靶点

• IC50: 0.28 μM (GAT-1), 137.34 μM (GAT-2), 202.8 μM (GAT-3)

体外研究

SKF89976A 具有较弱的抗痛觉异常作用。它在 CHO 细胞中稳定表达每种转运体的情况下，以底物摄取试验为方法，分别对血清素转运体（SERT）、去甲肾上腺素转运体（NET）和多巴胺转运体（DAT）进行抑制，IC50 值分别为 3514、202.13 和 728.8。SKF89976A 是 GABA-运输阻断剂。1 mM 的 GABA 引发了内向电流，该电流被 GABA 运输抑制剂 tiagabine（10 μM）和 SKF89976A（100 μM）完全抑制，但不受 100 μM picrotoxin 影响。100 μM 的 SKF89976-A 完全且可逆地阻断了 GABA 进入细胞的运输，从而消除了由背景 GABA 引发的内向电流。SKF89976A 是非运输型 GAT-1 阻断剂。它还抑制基底 GAT 激活引起的持续内向电流。在每项研究中，100 μM 的 SKF 89976-A 可使 GAT 电流平均减少 67.9±4.4%（n=19）。20 μM 的 SKF89976-A 能逐步降低并完全阻断由 GABA 引发的 GAT 电流，而不影响 GABAAR 介导的电流（n=4）。

体内研究

• 静脉注射 SKF89976A (0.3 mg/kg) 可产生较弱的抗痛觉异常反应。
• 在 PSL 模型小鼠中，腹膜内注射 SKF89976A 剂量依赖性地缓解了撤药阈值降低的现象。

反应信息

• 作为产物：
  描述：

  ethyl N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylate hydrochloride 在 盐酸 作用下， 反应 17.0h， 以65%的产率得到1-(4,4-二苯基-3-丁烯)-3-哌啶羧酸盐酸盐
  参考文献：
  名称：

  Orally Active and Potent Inhibitors of γ-Aminobutyric Acid Uptake

  摘要：

  3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].

  DOI：

  10.1021/jm50001a020

文献信息

• N-substituted azaheterocyclic carboxylic acids and their esters
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0066456B1

  公开（公告）日：1985-04-24
• US4383999A
  申请人：——

  公开号：US4383999A

  公开（公告）日：1983-05-17
• Orally Active and Potent Inhibitors of γ-Aminobutyric Acid Uptake
  作者：Fadia E. Ali、William E. Bondinell、Penelope A. Dandridge、James S. Frazee、Eleanor Garvey、Gerald R. Girard、Carl Kaiser、Thomas W. Ku、John J. Lafferty、George I. Moonsammy、Hye-Ja Oh、Julia A. Rush、Paulette E. Setler、Orum D. Stringer、Joseph W. Venslavsky、Beth W. Volpe、Libby M. Yunger、Charles L. Zirkle

  DOI：10.1021/jm50001a020

  日期：1985.5

  3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].