5-(1,2-dithiolan-3-yl)-1-(4-(4-fluorobenzyl)piperazin-1-yl)pentan-1-one | 1589517-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二硫杂环戊烷
• 英文名称: 5-(1,2-dithiolan-3-yl)-1-(4-(4-fluorobenzyl)piperazin-1-yl)pentan-1-one
• 英文别名: 5-(Dithiolan-3-yl)-1-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]pentan-1-one
• CAS: 1589517-86-1
• 化学式: C₁₉H₂₇FN₂OS₂
• 分子量: 382.567
• InChiKey: KELGQRKBRHZTRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  74.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1,2-dithiolan-3-yl)-1-(4-(4-fluorobenzyl)piperazin-1-yl)pentan-1-one 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-(1,2-dithiolan-3-yl)-1-[4-(4-fluorobenzyl)piperazin-1-yl]pentan-1-one chloride
  参考文献：
  名称：

  New bifunctional antioxidant/σ1 agonist ligands: Preliminary chemico-physical and biological evaluation

  摘要：

  We previously reported bifunctional sigma-1 (sigma(1)) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. sigma(1) and sigma(2) affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong sigma(1) affinity, displayed improved sigma(1) selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed sigma(1) agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on sigma(1) selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which sigma(1) receptor dysfunction and oxidative stress are contemporarily involved. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.05.045
• 作为产物：
  描述：

  1-(4-氟苄基)哌嗪 、 Thioctic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.17h， 生成 5-(1,2-dithiolan-3-yl)-1-(4-(4-fluorobenzyl)piperazin-1-yl)pentan-1-one
  参考文献：
  名称：

  New bifunctional antioxidant/σ1 agonist ligands: Preliminary chemico-physical and biological evaluation

  摘要：

  We previously reported bifunctional sigma-1 (sigma(1)) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. sigma(1) and sigma(2) affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong sigma(1) affinity, displayed improved sigma(1) selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed sigma(1) agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on sigma(1) selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which sigma(1) receptor dysfunction and oxidative stress are contemporarily involved. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.05.045

文献信息

• Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules
  作者：Beom-Cheol Kim、Seung-Hwan Lee、Mi Jang、Min Young Shon、Jeong Ho Park

  DOI：10.5012/bkcs.2013.34.11.3322

  日期：2013.11.20

  A series of hybrid molecules between ($\alpha}$)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE ($IC_50}=2.3\pm}0.7\mu}M$) and AChE ($IC_50}=30.31\pm}0.64\mu}M$). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $2.91\pm}0.15\mu}M$.

  合成了一系列（α-亚油酸（ALA）与苄基哌唑之间的杂合分子，并评估了它们的体外胆碱酯酶（乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE））抑制活性。尽管母体化合物对胆碱酯酶（ChE）没有表现出抑制活性，但所有杂合分子均显示出对BuChE的抑制活性。某些杂合化合物还表现出对AChE的抑制活性。具体来说，ALA-1-(3-甲基苄基)哌唑（15）被证明对BuChE（IC₅₀=2.3±0.7μM）和AChE（IC₅₀=30.31±0.64μM）均为有效的抑制剂。通过化合物15进行的抑制动力学研究显示为混合抑制类型。其对BuChE的结合亲和力（Kᵢ）值为2.91±0.15μM。