[2-氨基-4-((4-苄基哌嗪-1-基)甲基)-5-甲基噻吩-3-基](4-氯苯基)甲酮 | 1027493-16-8

• 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-苄基哌嗪-1-基)甲基)-5-甲基噻吩-3-基](4-氯苯基)甲酮
• 英文名称: [2-amino-4-((4-benzylpiperazin-1-yl)methyl)-5-methylthiophen-3-yl](4-chlorophenyl)methanone
• 英文别名: [2-Amino-4-[(4-benzylpiperazin-1-yl)methyl]-5-methylthiophen-3-yl]-(4-chlorophenyl)methanone
• CAS: 1027493-16-8
• 化学式: C₂₄H₂₆ClN₃OS
• 分子量: 440.009
• InChiKey: HYXHXEHHOZDASV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 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：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (2-氨基-4,5-二甲基-3-噻吩)(4-氯苯基)甲酮	(2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone	50508-66-2	C13H12ClNOS	265.763
  ——	2-[4-[(4-benzylpiperazin-1-yl)methyl]-3-(4-chlorobenzoyl)-5-methylthiophen-2-yl]isoindoline-1,3-dione	1394867-71-0	C32H28ClN3O3S	570.112
  ——	2-[3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl]isoindoline-1,3-dione	1027493-33-9	C21H14ClNO3S	395.866
  ——	2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-methylthiophen-2-yl]isoindoline-1,3-dione	1027493-34-0	C21H13BrClNO3S	474.762

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-苄基哌嗪-1-基)甲基)-5-甲基噻吩-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
• 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
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Olga Cruz-Lopez、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Allan R. Moorman、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1021/jm3007504

  日期：2012.9.13

  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.