2-[5-bromo-4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione | 1027493-30-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[5-bromo-4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione
• 英文别名: 2-[5-Bromo-4-(bromomethyl)-3-(4-chlorobenzoyl)thiophen-2-yl]isoindole-1,3-dione
• CAS: 1027493-30-6
• 化学式: C₂₀H₁₀Br₂ClNO₃S
• 分子量: 539.631
• InChiKey: ANMSCRSCVGLXHW-UHFFFAOYSA-N

物化性质

• 熔点：
  173-175 °C
• 沸点：
  698.6±65.0 °C(Predicted)
• 密度：
  1.848±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 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-[5-bromo-4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、413.69 kPa 条件下， 反应 3.0h， 以16%的产率得到2-[4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione
  参考文献：
  名称：

  Structure–activity relationships of 2-amino-3-aroyl-4-[(4-arylpiperazin-1-yl)methyl]thiophenes. Part 2: Probing the influence of diverse substituents at the phenyl of the arylpiperazine moiety on allosteric enhancer activity at the A1 adenosine receptor

  摘要：

  In a preliminary article, we reported the potent allosteric enhancer activity at the AI adenosine receptor of a small series of 2-amino-3-(4-chlorobenzoyl)-4[4-(aryl)piperazin-1-yl)methyl]thiophene derivatives bearing electron-withdrawing or electron-releasing groups at the para-position of the phenylpiperazine moiety. In the present study, we report the development of the compounds previously studied by modifying both the number and position of substituents on the phenylpiperazine moiety, aimed at establishing a structure-activity relationship identifying additional compounds with improved activity.The nature and the position of substituents on the phenyl ring tethered to the piperazine seemed to exert a fundamental influence on the allosteric enhancer activity, with the 3,4-difluoro 4i, 3-chloro-4-fluoro 4o, and 4-trifluoromethoxy 4ak derivatives being the most active compounds in binding (saturation and competition experiments) and functional cAMP studies. This study shows that it is also possible to obtain a good separation between allosteric enhancement and antagonistic activity at the A(1) adenosine receptor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.044
• 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) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 2.0h， 以90%的产率得到2-[5-bromo-4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione
  参考文献：
  名称：

  2-氨基-3-（4-氯苯甲酰基）-4- [N-（取代）哌嗪-1-基]噻吩作为A1腺苷受体有效变构增强剂的合成及生物学评估。

  摘要：

  描述了一系列2-氨基-3-（4-氯苯甲酰基）-4- [4-（烷基/芳基）哌嗪基-基]噻吩衍生物作为A 1-腺苷受体的变构增强剂的合成和评价。连接到哌嗪的苯环上取代基的性质似乎对变构增强剂活性产生根本影响，其中4-氯苯基8f和4-三氟甲基8j衍生物是结合中最活泼的化合物（饱和和置换实验）和功能性cAMP研究。

  DOI：

  10.1021/jm800586p

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。