N-(4-(ethylcarbamoyl)benzyl)-2,4-dihydroxy-5-isopropyl-N-methyl-benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-(ethylcarbamoyl)benzyl)-2,4-dihydroxy-5-isopropyl-N-methyl-benzamide
• 英文别名: N-[[4-(ethylcarbamoyl)phenyl]methyl]-2,4-dihydroxy-N-methyl-5-propan-2-ylbenzamide
• 化学式: C₂₁H₂₆N₂O₄
• 分子量: 370.448
• InChiKey: QTKFJMRRWITWJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-二羟基苯甲酸 在 aluminum (III) chloride 、 硫酸 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~120.0 ℃ 、3.0 MPa 条件下， 反应 81.0h， 生成 N-(4-(ethylcarbamoyl)benzyl)-2,4-dihydroxy-5-isopropyl-N-methyl-benzamide
  参考文献：
  名称：

  设计，合成和生物学评估一系列基于间苯二酚的N-苄基苯甲酰胺衍生物作为有效的Hsp90抑制剂

  摘要：

  热激蛋白90（Hsp90）是一种普遍存在的分子伴侣，负责许多致癌蛋白的稳定和成熟。因此，Hsp90已成为癌症化学疗法领域中有吸引力的靶标。在这项研究中，我们报告了一系列Hsp90抑制剂的设计，合成和生物学评估。特别是，化合物30F示出了显著的Hsp90 α与IC抑制活性50 5.3纳米的值和优异的生长抑制，GI 50值0.42μM的对非小细胞肺癌细胞，H1975。化合物30f有效降低了Hsp90客户蛋白（包括Her2，EGFR，Met，Akt和c-Raf）的表达水平。因此，复合30f促进了PARP，Caspase 3和Caspase 8的大量切割，表明30f通过凋亡途径诱导癌细胞死亡。此外，细胞色素P450分析表明化合物30f对五种主要P450亚型的活性具有弱抑制作用（ 对于1A2、2C9、2C19、2D6和3A，IC 50 > 5μM），表明30f与底物药物之间存在临床相互作用五种主要的

  DOI：

  10.1016/j.ejmech.2017.11.054

文献信息

• NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF
  申请人：INDUSTRY ACADEMIC COOPERATION FOUNDATION KEIMYUNG UNIVERSITY

  公开号：US20190031620A1

  公开（公告）日：2019-01-31

  The present invention relates to a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections.

  本发明涉及一种具有HSP90抑制活性或其药用盐的新化合物，以及其药用用途和包含二羟基苯化合物或苯甲酰胺化合物的组合物，该新化合物具有本发明的HSP90抑制活性，可以有效抑制HSP90，因此可以作为用于预防或治疗HSP90介导疾病的药物组合物或用于预防或改善HSP90介导疾病的保健功能食品，所述HSP90介导疾病包括癌症疾病、退行性神经疾病和病毒感染，从而有益地使用。
• Compound having HSP90 inhibitory activity or pharmaceutically acceptable salt thereof, and medical use thereof
  申请人：INDUSTRY ACADEMIC COOPERATION FOUNDATION KEIMYUNG UNIVERSITY

  公开号：US10464907B2

  公开（公告）日：2019-11-05

  The present invention relates to a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections.

  本发明涉及一种具有HSP90抑制活性的新型化合物或其药学上可接受的盐及其药用用途，以及包含二羟基苯基化合物或苯甲酰胺化合物的组合物，该组合物是具有本发明HSP90抑制活性的新型化合物，可有效抑制HSP90、因此可以有效地用作预防或治疗 HSP90 介导的疾病的药物组合物，或用作预防或改善 HSP90 介导的疾病的保健功能食品，这些疾病可从癌症疾病、退行性神经疾病和病毒感染组成的组中选出。
• Dihydroxybenzamide compound having HSP90 inhibitory activity or pharmaceutically acceptable salt thereof, and medical use thereof
  申请人：ONCOZEN CO., LTD.

  公开号：US10889552B2

  公开（公告）日：2021-01-12

  Disclosed is a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections.

  本发明公开了一种具有HSP90抑制活性的新型化合物或其药学上可接受的盐及其药用用途，以及包含二羟基苯基化合物或苯甲酰胺化合物的组合物，该组合物是一种具有本发明HSP90抑制活性的新型化合物，可有效抑制HSP90、因此可以有效地用作预防或治疗 HSP90 介导的疾病的药物组合物，或用作预防或改善 HSP90 介导的疾病的保健功能食品，这些疾病可从癌症疾病、退行性神经疾病和病毒感染组成的组中选出。
• [EN] NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF<br/>[FR] NOUVEAU COMPOSÉ AYANT UNE ACTIVITÉ INHIBITRICE DE HSP90 OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, ET UTILISATION MÉDICALE DE CELUI-CI<br/>[KO] HSP90 억제 활성을 갖는 신규 화합물 또는 이의 약제학적으로 허용가능한 염 및 이의 의학적 용도
  申请人：UNIV KEIMYUNG IND ACAD COOP FOUND

  公开号：WO2017131500A1

  公开（公告）日：2017-08-03

  HSP90 억제 활성을 갖는 신규 화합물 또는 이의 약제학적으로 허용가능한 염 및 이의 의학적 용도에 관한 것으로, 본 발명의 HSP90 억제 활성을 갖는 신규 화합물인 디히드록시페닐(dihydroxyphenyl)계 화합물 또는 벤즈아미드계 화합물을 포함하는 조성물은 HSP90을 효과적으로 억제할 수 있으므로, 암 질환, 퇴행성 신경질환 및 바이러스 감염증으로 이루어진 군에서 선택된 어느 하나의 HSP90 매개 질환 예방 또는 치료용 약학 조성물, 또는 HSP90 매개 질환 예방 또는 개선용 건강기능식품으로 유용하게 사용될 수 있다.
• Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors
  作者：Sun You Park、Yong Jin Oh、Yunmee Lho、Ju Hui Jeong、Kwang-Hyeon Liu、Jaeyoung Song、Soong-Hyun Kim、Eunyoung Ha、Young Ho Seo

  DOI：10.1016/j.ejmech.2017.11.054

  日期：2018.1

  Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α

  热激蛋白90（Hsp90）是一种普遍存在的分子伴侣，负责许多致癌蛋白的稳定和成熟。因此，Hsp90已成为癌症化学疗法领域中有吸引力的靶标。在这项研究中，我们报告了一系列Hsp90抑制剂的设计，合成和生物学评估。特别是，化合物30F示出了显著的Hsp90 α与IC抑制活性50 5.3纳米的值和优异的生长抑制，GI 50值0.42μM的对非小细胞肺癌细胞，H1975。化合物30f有效降低了Hsp90客户蛋白（包括Her2，EGFR，Met，Akt和c-Raf）的表达水平。因此，复合30f促进了PARP，Caspase 3和Caspase 8的大量切割，表明30f通过凋亡途径诱导癌细胞死亡。此外，细胞色素P450分析表明化合物30f对五种主要P450亚型的活性具有弱抑制作用（ 对于1A2、2C9、2C19、2D6和3A，IC 50 > 5μM），表明30f与底物药物之间存在临床相互作用五种主要的