2-amino-N-cyclopentyl-5-(2-oxo-2,3-dihydrothiazol-4-yl)benzenesulfonamide

• 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: 2-amino-N-cyclopentyl-5-(2-oxo-2,3-dihydrothiazol-4-yl)benzenesulfonamide
• 英文别名: 2-amino-N-cyclopentyl-5-(2-oxo-3H-1,3-thiazol-4-yl)benzenesulfonamide
• 化学式: C₁₄H₁₇N₃O₃S₂
• 分子量: 339.439
• InChiKey: IHFRTJBVIMIQHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲氧基乙酰氯 、 2-amino-N-cyclopentyl-5-(2-oxo-2,3-dihydrothiazol-4-yl)benzenesulfonamide 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以88%的产率得到N-(2-(N-cyclopentylsulfamoyl)-4-(2-oxo-2,3-dihydrothiazol-4-yl)phenyl)-2-methoxyacetamide
  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
• 作为产物：
  描述：

  3-乙酰胺基苯乙酮 在 吡啶 、 盐酸 、 硫酸 、 硝酸 、 铁粉 、 氯化铵 、 溶剂黄146 、 copper(ll) bromide 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 反应 2.0h， 生成 2-amino-N-cyclopentyl-5-(2-oxo-2,3-dihydrothiazol-4-yl)benzenesulfonamide
  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

• 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.