N-(2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl)-3-methoxybenzamide | 219125-63-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl)-3-methoxybenzamide
• 英文别名: N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide
• CAS: 219125-63-0
• 化学式: C₂₀H₂₄ClN₃O₂
• 分子量: 373.882
• InChiKey: DQVARXSGNFBPMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl)-3-methoxybenzamide 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以100%的产率得到{2-[4-(4-Chloro-phenyl)-piperazin-1-yl]-ethyl}-(3-methoxy-benzyl)-amine
  参考文献：
  名称：

  A Structure−Affinity Relationship Study on Derivatives of N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a High-Affinity and Selective D₄ Receptor Ligand

  摘要：

  N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1), a high-affinity and selective dopamine D-4 receptor ligand, was chosen as a lead, and structural modifications were done on its amide bond and on its alkyl chain linking the benzamide moiety to the piperazine ring and by preparing some semirigid analogues. The binding profile at dopamine D-4 and dopamine D-2, serotonin 5-HT1A, and adrenergic ar receptors of 16 new compounds was determined. From the results emerged that the modification of the amide bond and the elongation of the intermediate alkyl chain caused a decrease in dopamine D-4 receptor affinity. All prepared semirigid analogues displayed D-4 receptor affinity values in the same range of the opened counterparts.

  DOI：

  10.1021/jm991138z
• 作为产物：
  描述：

  3-甲氧基苯甲酸 、 4-(4-氯苯基)-1-哌嗪甲胺 在 三乙胺 、 氯甲酸甲酯 作用下， 生成 N-(2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl)-3-methoxybenzamide
  参考文献：
  名称：

  N- [2- [4-（4-氯苯基）哌嗪-1-基]乙基] -3-甲氧基苯甲酰胺：一种有效的选择性多巴胺D4配体。

  摘要：

  合成了一系列新的在烷基链上包含末端苯甲酰胺片段或四氢-1-基核的1-芳基-4-烷基哌嗪，并测试了在克隆的人多巴胺D4和D2受体亚型上的结合。本文讨论了对该系列的SAFIR（结构亲和关系）研究。N-ω-[4-芳基哌嗪-1-基]烷基]-甲氧基苯甲酰胺（化合物5、16-20）显示出最相关的D4受体亲和力，其IC50值在0.057至7.8 nM之间。其中，N- [2- [4-（4-氯苯基）哌嗪-1-基]乙基] -3-甲氧基苯甲酰胺（17）出现了，因为它对多巴胺D4受体表现出很高的亲和力（IC50 = 0.057 nM）。 D4相对于D2受体> 10000; 化合物17对5-羟色胺5-HT1A和肾上腺素α1受体也具有选择性。

  DOI：

  10.1021/jm981041x

文献信息

• Methods of Treating Disorders Associated with Protein Aggregation
  申请人：Pak Stephen C.

  公开号：US20130024953A1

  公开（公告）日：2013-01-24

  The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

  本发明涉及与蛋白质聚集相关的临床疾病的治疗方法，包括向受试者施用来自以下组中选择的抗蛋白质聚集（“APA”）化合物的有效量：哌唑酮，氟哌利多（例如氟哌利多盐酸盐），他莫昔芬（例如他莫昔芬柠檬酸盐），紫杉醇，蝉蜕素，蝉酸及其盐和结构相关化合物。本发明至少部分基于以下发现：上述每种化合物均能促进Caenorhabditis elegans模型系统中聚集的ATZ蛋白的降解。根据本发明，使用这些APA化合物之一或多个进行治疗，可用于缓解AT缺陷以及其他由蛋白质聚集标记的疾病的症状和体征，包括但不限于阿尔茨海默病、帕金森病和亨廷顿病。
• METHODS OF TREATING DISORDERS ASSOCIATED WITH PROTEIN AGGREGATION
  申请人：University Of Pittsburgh - of the Commonwealth System of Higher Education

  公开号：US20150265626A1

  公开（公告）日：2015-09-24

  The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

  本发明涉及治疗与蛋白质聚集相关的临床疾病的方法，包括向受试者施用来自以下组中选择的抗蛋白质聚集（“APA”）化合物的有效量：哌唑酮，氟苯奈嗪（例如，氟苯奈嗪盐酸盐），他莫昔芬（例如，他莫昔芬柠檬酸盐），紫杉醇，鲍鱼毒素，鲍鱼毒酸，其盐及其结构相关化合物。该发明至少部分基于以下发现：上述每种化合物均能够促进在秀丽隐杆线虫模型系统中聚集的ATZ蛋白质的降解。根据本发明，使用这些APA化合物中的一个或多个进行治疗可以用于改善AT缺乏症状和体征以及其他以蛋白质聚集为特征的疾病，包括但不限于阿尔茨海默病、帕金森病和亨廷顿病。
• METHODS FOR TREATING NEUROLOGICAL DISORDERS OR DAMAGE
  申请人：Tyers Mike

  公开号：US20090076019A1

  公开（公告）日：2009-03-19

  A clonogenic neurosphere assay is described that carries out high throughput screens (HTS) to identify potent and/or selective modulators of proliferation, differentiation and/or renewal of neural precursor cells, neural progenitor cells and/or self-renewing and multipotent neural stem cells (NSCs). Compositions comprising the identified modulators and methods of using the modulators and compositions, in particular to treat neurological disorders (e.g. brain or CNS cancer) or damage are also disclosed.
• AUTOMATED HIGH-CONTENT LIVE ANIMAL DRUG SCREENING USING C. ELEGANS
  申请人：University of Pittsburgh - of the Commonwealth System of Higher Education

  公开号：US20140331341A1

  公开（公告）日：2014-11-06

  The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.
• US8058243B2
  申请人：——

  公开号：US8058243B2

  公开（公告）日：2011-11-15