(S)-N-(1-(5-iodo-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide | 1609191-10-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-N-(1-(5-iodo-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide
• 英文别名: N-[(1S)-1-(5-iodo-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl]-1,3-thiazole-5-carboxamide
• CAS: 1609191-10-7
• 化学式: C₁₅H₂₀IN₅O₂S
• 分子量: 461.327
• InChiKey: QSTPKLXGQABIDY-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-N-(1-(5-iodo-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 生成 N-(1-(5-(isoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide mono L-tartrate salt
  参考文献：
  名称：

  Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs

  摘要：

  The identification of a new series of P. falciparum growth inhibitors is described. Starting from a series of known human class I HDAC inhibitors a SAR exploration based on growth inhibitory activity in parasite and human cells-based assays led to the identification of compounds with submicromolar inhibition of P. falciparum growth (EC50 < 500 nM) and good selectivity over the activity of human HDAC in cells (up to >50-fold). Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies.

  DOI：

  10.1021/acsmedchemlett.5b00468
• 作为产物：
  描述：

  (S)-benzyl (1-(5-iodo-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)carbamate 在 氢溴酸 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 (S)-N-(1-(5-iodo-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide
  参考文献：
  名称：

  [EN] COMPOUNDS FOR USE IN THE TREATMENT OF PARASITIC DISEASES
  [FR] COMPOSÉS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES PARASITAIRES

  摘要：

  本发明涉及用于治疗寄生虫病的化合物，这些疾病是由寄生虫引起或传播的传染病。本发明的化合物对疟疾病原体特别活跃。这些化合物是寄生虫组蛋白去乙酰化酶（PfHDAC）的选择性抑制剂，能够抑制寄生虫（如疟原虫）的生长，且所需浓度低于抑制哺乳动物细胞生长所需的浓度。

  公开号：

  WO2014067985A1

文献信息

• Improved Selective Class I HDAC and Novel Selective HDAC3 Inhibitors: Beyond Hydroxamic Acids and Benzamides
  作者：Alberto Bresciani、Jesus M. Ontoria、Ilaria Biancofiore、Antonella Cellucci、Alina Ciammaichella、Annalise Di Marco、Federica Ferrigno、Alessandra Francone、Savina Malancona、Edith Monteagudo、Emanuela Nizi、Paola Pace、Simona Ponzi、Ilaria Rossetti、Maria Veneziano、Vincenzo Summa、Steven Harper

  DOI：10.1021/acsmedchemlett.8b00517

  日期：2019.4.11

  application of class I HDAC inhibitors as cancer therapies is well established, but more recently their development for nononcological indications has increased. We report here on the generation of improved class I selective human HDAC inhibitors based on an ethylketone zinc binding group (ZBG) in place of the hydroxamic acid that features the majority of HDAC inhibitors. We also describe a novel set

  I类HDAC抑制剂作为癌症疗法的应用已广为人知，但最近它们在非肿瘤适应症方面的开发有所增加。我们在此报告基于乙基酮锌结合基团（ZBG）代替具有大多数HDAC抑制剂特征的异羟肟酸的改进I类选择性人HDAC抑制剂的产生。我们还描述了一组新的HDAC3同种型选择性抑制剂，与最常用的HDAC3选择性工具化合物RGFP966相比，它们具有更强的效力和选择性。这些化合物还是基于迄今为止报道的HDAC3选择性化合物中邻位苯胺的替代ZBG 。
• Compounds for use in the treatment of parasitic diseases
  申请人：IRBM—SCIENCE PARK S.P.A.

  公开号：US09365541B2

  公开（公告）日：2016-06-14

  The present invention relates to compounds useful for treating parasitic diseases, which are infectious diseases caused or transmitted by a parasite. Compounds of the invention are particularly active against the causative pathogens in malaria. Such compounds are selective inhibitors of parasitic histone deacetylase (PfHDAC) and suppress the growth of parasites, such as Plasmodium falciparum, at a lower concentration than the concentration required for the inhibition of the growth of mammalian cells.

  本发明涉及用于治疗寄生虫病的化合物，这些疾病是由寄生虫引起或传播的传染性疾病。本发明的化合物特别活跃于疟疾的病原体。这些化合物是寄生虫组蛋白去乙酰化酶（PfHDAC）的选择性抑制剂，可以在比抑制哺乳动物细胞生长所需浓度更低的浓度下抑制寄生虫（如疟原虫）的生长。
• COMPOUNDS FOR USE IN THE TREATMENT OF PARASITIC DISEASES
  申请人：IRBM - SCIENCE PARK S.P.A.

  公开号：US20150299163A1

  公开（公告）日：2015-10-22

  The present invention relates to compounds useful for treating parasitic diseases, which are infectious diseases caused or transmitted by a parasite. Compounds of the invention are particularly active against the causative pathogens in malaria. Such compounds are selective inhibitors of parasitic histone deacetylase (PfHDAC) and suppress the growth of parasites, such as Plasmodium falciparum , at a lower concentration than the concentration required for the inhibition of the growth of mammalian cells.

  本发明涉及用于治疗寄生虫病的化合物，这些疾病是由寄生虫引起或传播的传染病。本发明的化合物特别对疟疾病原体具有活性。这些化合物是寄生虫组蛋白去乙酰化酶(PfHDAC)的选择性抑制剂，可以在比抑制哺乳动物细胞生长所需浓度更低的浓度下抑制疟原虫等寄生虫的生长。
• US9365541B2
  申请人：——

  公开号：US9365541B2

  公开（公告）日：2016-06-14