2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-phenylthiophen-2-yl]isoindoline-1,3-dione | 1027493-42-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-phenylthiophen-2-yl]isoindoline-1,3-dione
• 英文别名: 2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-phenylthiophen-2-yl]isoindole-1,3-dione；2-[4-(Bromomethyl)-3-(4-chlorobenzoyl)-5-phenylthiophen-2-yl]isoindole-1,3-dione
• CAS: 1027493-42-0
• 化学式: C₂₆H₁₅BrClNO₃S
• 分子量: 536.833
• InChiKey: SEMWIZBPNQYTFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-phenylthiophen-2-yl]isoindoline-1,3-dione 在 一水合肼 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 [2-Amino-5-phenyl-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone
  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
• 作为产物：
  描述：

  2-[3-(4-chlorobenzoyl)-5-bromo-4-methylthiophen-2-yl]isoindoline-1,3-dione 在 N-溴代丁二酰亚胺(NBS) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 cesium fluoride 、 过氧化苯甲酰 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 8.5h， 生成 2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-phenylthiophen-2-yl]isoindoline-1,3-dione
  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

• Synthesis and biological effects of novel 2-amino-3-(4-chlorobenzoyl)-4-substituted thiophenes as allosteric enhancers of the A1 adenosine receptor
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Allan R. Moorman、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1016/j.ejmech.2013.07.002

  日期：2013.9

  fused indole nuclei corresponding to 1,2,3,4-tetrahydropyrazino[1,2-a]indole, 1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole, tetrahydro-γ-carboline, tetrahydroisoquinoline, spiro-1,3-benzodioxolepiperidine, aliphatic tertiary amine, N-alkylaniline, aryl ether and aryl thioether templates. The 1,2,3,4-tetrahydropyrazino[1,2-a]indole derivatives 3a–c and 3e were the most active compounds in binding (saturation

  A 1腺苷受体的变构增强剂代表一种新颖且独特的药物设计策略，可以以位点和事件特定的方式增强对内源性腺苷的反应。我们先前已经研究了围绕一系列2-氨基-3-芳酰基-4-[（4-芳基哌嗪-1-基）甲基]噻吩衍生物作为A 1腺苷受体的有效变构增强剂的详细的结构-活性关系研究。。在这份手稿中，我们报告了我们对2-氨基-3-（4-氯苯甲酰基）-噻吩系统的4-位进一步取代对变构增强剂活性的影响的研究，以探索通过用芳基哌嗪部分取代芳基哌嗪部分来测定体积耐受性1,2,3,4-四氢吡嗪并[1,2- a]的一系列稠合吲哚核]吲哚，1,2,3,4,10,10a-六氢吡嗪并[1,2- a ]吲哚，四氢-γ-咔啉，四氢异喹啉，螺-1,3-苯并二氧戊哌啶，脂族叔胺，N-烷基苯胺，芳基醚和芳基硫醚模板。1,2,3,4-四氢吡嗪并[1,2- a ]吲哚衍生物3a – c和3e是结合（饱和和竞争）和功能性cAMP研究中最活跃的化合物，能够增强激动剂[
• ALLOSTERIC ENHANCERS OF THE A1 ADENOSINE RECEPTOR
  申请人：Baraldi Pier Giovanni

  公开号：US20090281145A1

  公开（公告）日：2009-11-12

  The present invention provides compounds of formula (I) wherein W, R 1 , R 5 and R 6 have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric enhancers 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, and inflammatory pain, cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke, neurological disease or injury, sleep disorders, epilepsy and depression.

  本发明提供了式(I)的化合物 其中W，R1，R5和R6在本说明书中定义的含义。式(I)的化合物是A1腺苷受体的变构增强剂，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，特别是神经病性疼痛、炎症性疼痛、心脏疾病或紊乱，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，神经疾病或损伤，睡眠障碍，癫痫和抑郁症的治疗。
• 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。
• Allosteric Enhancers of th A1 Adenosine Receptor
  申请人：Baraldi Pier Giovanni

  公开号：US20120108636A1

  公开（公告）日：2012-05-03

  The present invention provides compounds of formula (I) wherein W, R 1 , R 5 and R 6 have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric enhancers 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, and inflammatory pain, cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke, neurological disease or injury, sleep disorders, epilepsy and depression.

  本发明提供了式（I）化合物，其中W、R1、R5和R6的含义如本规范中所定义。式（I）化合物是A1腺苷受体的别构增强剂，因此可以用于治疗由A1腺苷受体介导的疾病。因此，式（I）化合物可以用于治疗疼痛，特别是神经病理性疼痛和炎症性疼痛，心脏疾病或疾病，如心脏心律失常，例如阵发性室上性心动过速，心绞痛，心肌梗塞和中风，神经系统疾病或损伤，睡眠障碍，癫痫和抑郁症。