5-acetyl-2-fluorobenzenesulfonyl chloride | 1181772-21-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-acetyl-2-fluorobenzenesulfonyl chloride
• 英文别名: 3'-chlorosulfonyl-4'-fluoroacetophenone
• CAS: 1181772-21-3
• 化学式: C₈H₆ClFO₃S
• mdl: MFCD11919069
• 分子量: 236.651
• InChiKey: HVMVYNHFPJHPQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  59.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-acetyl-2-fluorobenzenesulfonyl chloride 在 tetra-N-butylammonium tribromide 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  2-羟基苯甲酸衍生物作为选择性 SIRT5 抑制剂的鉴定

  摘要：

  sirtuin 脱乙酰酶 SIRT5 在调节多种代谢途径中起着重要作用，并可能代表治疗多种人类疾病（尤其是癌症）的有吸引力的靶标。在这项研究中，我们报告了通过我们的中等通量热转移筛选试验将带有 2-羟基苯甲酸官能团的命中化合物11鉴定为新型 SIRT5 选择性抑制剂。Hit 11以剂量依赖性方式稳定 SIRT5，并在基于胰蛋白酶偶联酶的测定中显示出对 SIRT5 的中度抑制活性和对 SIRT1、2 和 3 的高亚型选择性。11的羧酸和相邻的羟基对于维持活性至关重要。进一步提高化合物11的效力, 进行了先导优化，导致化合物43 的效力提高了 10 倍。总的来说，化合物11代表了一种有前途的新化学支架，可用于进一步研究以开发 SIRT5 选择性抑制剂。

  DOI：

  10.1016/j.ejmech.2022.114623
• 作为产物：
  描述：

  4'-氟-3'-硝基苯乙酮 在 盐酸 、 铁粉 、 氯化铵 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 生成 5-acetyl-2-fluorobenzenesulfonyl chloride
  参考文献：
  名称：

  Fragment-Based Drug Discovery of 2-Thiazolidinones as BRD4 Inhibitors: 2. Structure-Based Optimization

  摘要：

  The signal transduction of acetylated histone can be processed through a recognition module, bromodomain. Several inhibitors targeting BRD4, one of the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery and optimization of a new series of 2-thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided by crystal structure analysis, we reversed the sulfonamide group and identified a new binding mode. A structure-activity relationship study on this new series led to several potent BRD4 inhibitors with IC50 of about 0.05-0.1 mu M in FP binding assay and GI50 of 0.1-0.3 mu M in cell based assays. To complete the lead-like assessment of this series, we further checked its effects on BRD4 downstream protein c-Myc, investigated its selectivity among five different bromodomain proteins, as well as the metabolic stability test, and reinforced the utility of 2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anticancer drug development.

  DOI：

  10.1021/jm501504k

文献信息

• Thiazolidine derivatives
  申请人：Hoechst Aktiengesellschaft

  公开号：US04061761A1

  公开（公告）日：1977-12-06

  The invention relates to thiazolidine derivatives having in 4-position a hydroxy group and a 3'-sulphamyl-phenyl substituent, in 2-position an imino group and in 1-position an aliphatic or cycloaliphatic substituent. Said thiazolidines have diuretic activity. The invention also relates to a process for the manufacture of said compounds.

  本发明涉及在4位具有羟基和3'-磺酰氨基-苯基取代基，在2位具有亚氨基，在1位具有脂肪族或环脂肪族取代基的噻唑烷衍生物。所述噻唑烷具有利尿活性。本发明还涉及制造所述化合物的方法。
• US4061761A
  申请人：——

  公开号：US4061761A

  公开（公告）日：1977-12-06
• US4125614A
  申请人：——

  公开号：US4125614A

  公开（公告）日：1978-11-14
• Fragment-Based Drug Discovery of 2-Thiazolidinones as BRD4 Inhibitors: 2. Structure-Based Optimization
  作者：Lele Zhao、Yingqing Wang、Danyan Cao、Tiantian Chen、Qi Wang、Yanlian Li、Yechun Xu、Naixia Zhang、Xin Wang、Danqi Chen、Lin Chen、Yue-Lei Chen、Guangxin Xia、Zhe Shi、Yu-Chih Liu、Yijyun Lin、Zehong Miao、Jingkang Shen、Bing Xiong

  DOI：10.1021/jm501504k

  日期：2015.2.12

  The signal transduction of acetylated histone can be processed through a recognition module, bromodomain. Several inhibitors targeting BRD4, one of the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery and optimization of a new series of 2-thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided by crystal structure analysis, we reversed the sulfonamide group and identified a new binding mode. A structure-activity relationship study on this new series led to several potent BRD4 inhibitors with IC50 of about 0.05-0.1 mu M in FP binding assay and GI50 of 0.1-0.3 mu M in cell based assays. To complete the lead-like assessment of this series, we further checked its effects on BRD4 downstream protein c-Myc, investigated its selectivity among five different bromodomain proteins, as well as the metabolic stability test, and reinforced the utility of 2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anticancer drug development.
• Identification of 2-hydroxybenzoic acid derivatives as selective SIRT5 inhibitors
  作者：Yanghan Liu、Bikash Debnath、Surinder Kumar、David B. Lombard、Nouri Neamati

  DOI：10.1016/j.ejmech.2022.114623

  日期：2022.11

  especially cancer. In this study, we report the identification of the hit compound 11 bearing a 2-hydroxybenzoic acid functional group as a novel SIRT5-selective inhibitor via our medium-throughput thermal shift screening assay. Hit 11 stabilizes SIRT5 in a dose-dependent manner and shows moderate inhibitory activity against SIRT5 and high subtype selectivity over SIRT1, 2, and 3 in a trypsin coupled enzyme-based

  sirtuin 脱乙酰酶 SIRT5 在调节多种代谢途径中起着重要作用，并可能代表治疗多种人类疾病（尤其是癌症）的有吸引力的靶标。在这项研究中，我们报告了通过我们的中等通量热转移筛选试验将带有 2-羟基苯甲酸官能团的命中化合物11鉴定为新型 SIRT5 选择性抑制剂。Hit 11以剂量依赖性方式稳定 SIRT5，并在基于胰蛋白酶偶联酶的测定中显示出对 SIRT5 的中度抑制活性和对 SIRT1、2 和 3 的高亚型选择性。11的羧酸和相邻的羟基对于维持活性至关重要。进一步提高化合物11的效力, 进行了先导优化，导致化合物43 的效力提高了 10 倍。总的来说，化合物11代表了一种有前途的新化学支架，可用于进一步研究以开发 SIRT5 选择性抑制剂。