7-(1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide | 1179813-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 7-(1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide
• 英文别名: 7-(1H-benzimidazol-2-yl)-N-hydroxyheptanamide
• CAS: 1179813-27-4
• 化学式: C₁₄H₁₉N₃O₂
• 分子量: 261.324
• InChiKey: XUKAVFWFVUQTCG-UHFFFAOYSA-N

物化性质

• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-溴-2-硝基苯胺 在 dihydroxyborane 、 四(三苯基膦)钯 、 palladium on activated charcoal 、 盐酸羟胺 、 甲酸铵 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 7-(1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide
  参考文献：
  名称：

  Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents

  摘要：

  A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.001

文献信息

• Cap-Modified Hydroxamate Analogues as Histone Deacetylases Inhibitors and Antitumor Agents
  作者：Qing-Wei Zhang、Juan Feng、Jian-Qi Li

  DOI：10.5012/bkcs.2014.35.1.129

  日期：2014.1.20

  Two series of SAHA-liked hydroxamate analogues were designed, synthesized and evaluated for their biological activities against nuclear HDACs. Compounds of Series I were found to be very effective inhibitors of cancer cell growth in the PC-3, Hut78, K562 and Jurkat E6-1 cancer cell lines with mean $IC_50}$ values from $0.54\mu}M$ (Ic, Jurkat E6-1) to $7.73\mu}M$ (Ib, K562), indicating that they are cell permeable and the benzimidazolyl-based ligands are flexible enough to occupy the binding site of HDAC.

  两系列类似于SAHA的羟肟酸类似物被设计、合成并评估了它们对核HDACs的生物活性。第一系列化合物被发现对PC-3、Hut78、K562和Jurkat E6-1肿瘤细胞系具有非常有效的抑制生长作用，其平均$IC_50}$值从$0.54\mu}M$（Ic，Jurkat E6-1）至$7.73\mu}M$（Ib，K562），表明这些化合物具有细胞通透性，且苯并咪唑基的配体足够柔韧以占据HDAC的结合位点。
• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE OF HYDROXAMIC ACID DERIVATIVES<br/>[FR] COMPOSÉS, COMPOSITIONS PHARMACEUTIQUES ET PROCÉDÉS D'UTILISATION DE DÉRIVÉS D'ACIDE HYDROXAMIQUE
  申请人：TRANSLATIONAL GENOMICS RES INST

  公开号：WO2009100045A1

  公开（公告）日：2009-08-13

  The invention encompasses a compound derived from hydroxamic acid that may be used to slow the expansion of cancer cells and thus is effective in the treatment of cancer. Generally, the disclosed compound includes a benzimidazole group coupled to a hydroxyamide of five or more unsubstituted carbon atoms and any pharmaceutically acceptable salts, solvates and chemically protected forms thereof. Also disclosed are pharmacological compositions including the compound and methods of using the compound to slow the expansion of cancer cells as well as methods of using the compound to treat cancer.

  该发明涵盖了一种源自羟羧酸的化合物，可以用来减缓癌细胞的扩张，因此在癌症治疗中有效。通常，所披露的化合物包括与苯并咪唑基团偶联的含有五个或更多未取代碳原子的羟基酰胺，以及任何药用可接受的盐、溶剂化合物和其化学保护形式。还披露了包括该化合物的药理学组合物以及使用该化合物减缓癌细胞扩张的方法，以及使用该化合物治疗癌症的方法。
• A direct alkylation route to branched derivatives of suberoylanilide hydroxamic acid (SAHA), a potent non-selective inhibitor of histone deacetylases
  作者：Jonathan A. Dines、Charles M. Marson

  DOI：10.1016/j.tet.2016.11.039

  日期：2016.12

  Alkylation of malonamic esters provides a direct approach to derivatives of suberoylanilide hydroxamic acid (SAHA) that are branched at the amide carbon atom, a location pivotal for enhancing biological and therapeutic activity. Alkylations use NaH in THF followed by addition of the ester of 6-bromohexanoic acid; no protection of the amidic NH group is necessary. By this means, carboxylic acid, ester

  丙二酸酯的烷基化提供了直接亚酰胺基异羟肟酸衍生物（SAHA）的直接方法，该衍生物分支在酰胺碳原子上，酰胺碳原子是增强生物学和治疗活性的关键位置。烷基化反应使用NaH在THF中的溶液，然后加入6-溴己酸的酯；不需要保护酰胺基NH基。通过这种方法，已经将羧酸，酯，酰胺，羟甲基和2-苯并咪唑基支化单元连接到SAHA主链上。已经开发了一次改变一个分支单元的途径。
• COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE OF HYDROXAMIC ACID DERIVATIVES
  申请人：Wang Tong

  公开号：US20120053188A1

  公开（公告）日：2012-03-01

  The invention encompasses a compound derived from hydroxamic acid that may be used to slow the expansion of cancer cells and thus is effective in the treatment of cancer. Generally, the disclosed compound includes a benzimidazole group coupled to a hydroxyamide of five or more unsubstituted carbon atoms and any pharmaceutically acceptable salts, solvates and chemically protected forms thereof. Also disclosed are pharmacological compositions including the compound and methods of using the compound to slow the expansion of cancer cells as well as methods of using the compound to treat cancer.

  这项发明涵盖了一种源自羟肟酸的化合物，可用于减缓癌细胞的扩张，因此在癌症治疗中是有效的。一般而言，所披露的化合物包括一个苯并咪唑基团与五个或更多未取代碳原子的羟酰胺偶联而成，以及任何药学上可接受的盐、溶剂化物和化学保护形式。还披露了包括该化合物的药理学组合物以及使用该化合物减缓癌细胞扩张的方法以及使用该化合物治疗癌症的方法。
• US8987468B2
  申请人：——

  公开号：US8987468B2

  公开（公告）日：2015-03-24