Naphthalene-2-sulfonic acid [4-(2-bromo-acetyl)-phenyl]-amide | 872373-39-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Naphthalene-2-sulfonic acid [4-(2-bromo-acetyl)-phenyl]-amide
• 英文别名: N-[4-(2-bromoacetyl)phenyl]naphthalene-2-sulfonamide
• CAS: 872373-39-2
• 化学式: C₁₈H₁₄BrNO₃S
• 分子量: 404.284
• InChiKey: OMKGWBHSWAKXCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Naphthalene-2-sulfonic acid [4-(2-bromo-acetyl)-phenyl]-amide 、 potassium thioacetate 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 S-[2-[4-(naphthalen-2-ylsulfonylamino)phenyl]-2-oxoethyl] ethanethioate
  参考文献：
  名称：

  α-Mercaptoketone based histone deacetylase inhibitors

  摘要：

  In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.058
• 作为产物：
  描述：

  N-(4-acetylphenyl)naphthalene-2-sulfonamide 在 phenyltrimethylammonium tribromide 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 Naphthalene-2-sulfonic acid [4-(2-bromo-acetyl)-phenyl]-amide
  参考文献：
  名称：

  Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators

  摘要：

  Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 mu M to 0.81 mu M against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.023

文献信息

• US7470722B2
  申请人：——

  公开号：US7470722B2

  公开（公告）日：2008-12-30
• [EN] MULTICYCLIC SULFONAMIDE COMPOUNDS AS INHIBITORS OF HISTONE DEACETYLASE FOR THE TREATMENT OF DISEASE<br/>[FR] COMPOSES SULFONAMIDE MULTICYCLIQUES INHIBANT L'HISTONE DESACETYLASE POUR LE TRAITEMENT DE MALADIE
  申请人：KALYPSYS INC

  公开号：WO2005123089A2

  公开（公告）日：2005-12-29

  Disclosed herein are carbonyl compounds of Formula (I) as described herein. Methods and compositions are disclosed for treating disease states including, but not limited to cancers, autoimmune diseases, tissue damage, central nervous system disorders, neurodegenerative disorders, fibrosis, bone disorders, polyglutamine-repeat disorders, anemias, thalassemias, inflammatory conditions, cardiovascular conditions, and disorders in which angiogenesis play a role in pathogenesis, using the compounds of the invention. In addition, methods of modulating the activity of histone deacetylase (HDAC) are also disclosed.
• Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
  作者：Ridong Li、Xianling Ning、Shuo Zhou、Zhiqiang Lin、Xingyu Wu、Hong Chen、Xinyu Bai、Xin Wang、Zemei Ge、Runtao Li、Yuxin Yin

  DOI：10.1016/j.ejmech.2017.11.023

  日期：2018.1

  Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 mu M to 0.81 mu M against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. (C) 2017 Elsevier Masson SAS. All rights reserved.
• α-Mercaptoketone based histone deacetylase inhibitors
  作者：Paul L. Wash、Timothy Z. Hoffman、Brandon M. Wiley、Céline Bonnefous、Nicholas D. Smith、Michael S. Sertic、Charles M. Lawrence、Kent T. Symons、Phan-Manh Nguyen、Kevin D. Lustig、Xin Guo、Tami Annable、Stewart A. Noble、Jeffrey H. Hager、Christian A. Hassig、James W. Malecha

  DOI：10.1016/j.bmcl.2008.10.058

  日期：2008.12

  In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo. (C) 2008 Elsevier Ltd. All rights reserved.