{2-氨基-4-[(4-(4-氟苯基)哌嗪-1-基)甲基]-5-乙基-噻吩-3-基}(4-氯苯基)甲酮 | 1027493-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: {2-氨基-4-[(4-(4-氟苯基)哌嗪-1-基)甲基]-5-乙基-噻吩-3-基}(4-氯苯基)甲酮
• 英文名称: {2-Amino-5-ethyl-4-[(4-(4-fluorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone
• 英文别名: {2-amino-4-[(4-(4-fluorophenyl)piperazin-1-yl)methyl]-5-ethyl-thiophen-3-yl}(4-chlorophenyl)methanone；[2-Amino-5-ethyl-4-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone
• CAS: 1027493-23-7
• 化学式: C₂₄H₂₅ClFN₃OS
• 分子量: 457.999
• InChiKey: HLQHCKAEUVYEJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氯苯乙酰腈 在 N-溴代丁二酰亚胺(NBS) 、 sulfur 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 、 乙腈 为溶剂， 反应 26.0h， 生成 {2-氨基-4-[(4-(4-氟苯基)哌嗪-1-基)甲基]-5-乙基-噻吩-3-基}(4-氯苯基)甲酮
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-Amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-Modification on Allosteric Enhancer Activity at the A₁ Adenosine Receptor

  摘要：

  We have recently reported a detailed structure activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]thiophene derivatives as potent allosteric enhancers of the A(1) adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments.

  DOI：

  10.1021/jm3007504

文献信息

• ALLOSTERIC MODULATORS OF THE A1 ADENOSINE RECEPTOR
  申请人：Baraldi Pier Giovanni

  公开号：US20080119460A1

  公开（公告）日：2008-05-22

  The present invention provides compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 and Q have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric modulators of the A 1 adenosine receptor and, thus, may be employed for the treatment of conditions mediated by the A 1 adenosine receptor. Accordingly, the compounds of formula (I) may be employed for treatment of pain, in particular, chronic pain such as neuropathic pain; cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke; neurological disease or injury; sleep disorder; epilepsy; and depression.

  本发明提供了式（I）的化合物，其中R1、R2、R3、R4和Q在本说明书中有定义。式（I）的化合物是A1腺苷受体的变构调节剂，因此可用于治疗由A1腺苷受体介导的疾病。因此，式（I）的化合物可用于治疗疼痛，特别是慢性疼痛如神经病痛；心脏疾病或紊乱，如心律失常，如阵发性室上性心动过速，心绞痛，心肌梗死和中风；神经系统疾病或损伤；睡眠障碍；癫痫；和抑郁症。
• Allosteric Modulators of the A1 Adenosine Receptor
  申请人：Baraldi Pier Giovanni

  公开号：US20110053917A1

  公开（公告）日：2011-03-03

  The present invention provides compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 and Q have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric modulators of the A 1 adenosine receptor and, thus, may be employed for the treatment of conditions mediated by the A l adenosine receptor. Accordingly, the compounds of formula (I) may be employed for treatment of pain, in particular, chronic pain such as neuropathic pain; cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke; neurological disease or injury; sleep disorder; epilepsy; and depression.

  本发明提供了公式（I）的化合物，其中R1、R2、R3、R4和Q的含义如规范中所定义。公式（I）的化合物是A1腺苷受体的别构调节剂，因此可用于治疗由A1腺苷受体介导的疾病。因此，公式（I）的化合物可用于治疗疼痛，特别是神经病理性疼痛；心脏疾病或障碍，如心律失常，例如阵发性室上性心动过速，心绞痛，心肌梗死和中风；神经系统疾病或损伤；睡眠障碍；癫痫；和抑郁症。
• US7855209B2
  申请人：——

  公开号：US7855209B2

  公开（公告）日：2010-12-21
• US7897596B2
  申请人：——

  公开号：US7897596B2

  公开（公告）日：2011-03-01
• [EN] ALLOSTERIC MODULATORS OF THE A1 ADENOSINE RECEPTOR<br/>[FR] MODULATEURS ALLOSTÉRIQUES DU RÉCEPTEUR DE L'ADÉNOSINE A1
  申请人：KING PHARMACEUTICALS RES & DEV

  公开号：WO2008063984A2

  公开（公告）日：2008-05-29

  [EN] The present invention provides compounds of formula (I) wherein R₁, R₂, R₃, R₄ and Q have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric modulators of the A₁ adenosine receptor and, thus, may be employed for the treatment of conditions mediated by the A₁ adenosine receptor. Accordingly, the compounds of formula (I) may be employed for treatment of pain, in particular, chronic pain such as neuropathic pain; cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke; neurological disease or injury; sleep disorder; epilepsy; and depression.
  [FR] La présente invention concerne des composés représentés par la formule (I) dans laquelle R₁, R₂, R₃, R₄ and Q présentent une signification telle que définie dans la description. Les composés représentés par la formule (I) sont des modulateurs allostériques du récepteur de l'adénosine A1 et, par conséquent, peuvent être utilisés pour le traitement d'états médiés par le récepteur de l'adénosine A1. Ainsi, les composés représentés par la formule (I) peuvent être utilisés pour le traitement de douleurs, en particulier, de douleurs chroniques telle que les douleurs neuropathiques; de maladies ou de troubles cardiaques tels que les dysrythmies cardiaques, par ex., la tachycardie supraventriculaire paroxystique, l'angor, l'infarctus du myocarde et l'accident cérébrovasculaire; de maladies ou de lésions neurologiques; de troubles du sommeil, de l'épilepsie; et de la dépression.