N-(4-(4-methylthiazol-5-yl)benzyl)acetamide | 1485065-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(4-(4-methylthiazol-5-yl)benzyl)acetamide
• 英文别名: N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]acetamide
• CAS: 1485065-66-4
• 化学式: C₁₃H₁₄N₂OS
• 分子量: 246.333
• InChiKey: PLCJTEQSRQOJTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴苯腈 在 sodium tetrahydroborate 、 N,N-二甲基乙酰胺 、 potassium acetate 、 palladium diacetate 、 三乙胺 、 cobalt(II) chloride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 18.17h， 生成 N-(4-(4-methylthiazol-5-yl)benzyl)acetamide
  参考文献：
  名称：

  Is NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein–Protein Interactions?

  摘要：

  Modulation of protein-protein interactions (PPIs) with small molecules has been hampered by a lack of lucid methods capable of reliably identifying high-quality hits. In fragment screening, the low ligand efficiencies associated with PPI target sites pose significant challenges to fragment binding detection. Here, we investigate the requirements for ligand-based NMR techniques to detect rule-of-three compliant fragments that form part of known high affinity inhibitors of the PPI between the von Hippel-Lindau protein and the alpha subunit of hypoxia-inducible factor 1 (pVHL:HIF-1 alpha). Careful triaging allowed rescuing weak but specific binding of fragments that would otherwise escape detection at this PPI. Further structural information provided by saturation transfer difference (STD) group epitope mapping, protein-based NMR, competitive isothermal titration calorimetry (ITC), and X-ray crystallography confirmed the binding mode of the rescued fragments. Our findings have important implications for PPI druggability assessment by fragment screening as they reveal an accessible threshold for fragment detection and validation.

  DOI：

  10.1021/ml400296c

文献信息

• [EN] STAT DEGRADERS AND USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE STAT ET LEURS UTILISATIONS
  申请人：KYMERA THERAPEUTICS INC

  公开号：WO2020206424A1

  公开（公告）日：2020-10-08

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用方法。
• [EN] DEGRADATION AGENTS FOR CYCLIN DEPENDENT KINASE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF AND USE THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE KINASE DÉPENDANTE DE LA CYCLINE, LEUR PROCÉDÉ DE PRÉPARATION, COMPOSITION PHARMACEUTIQUE DE CEUX-CI ET UTILISATION ASSOCIÉE<br/>[ZH] 一类细胞周期依赖性激酶的降解剂、其制备方法、药物组合物及其用途
  申请人：SHANGHAI INST MATERIA MEDICA CAS

  公开号：WO2020035049A1

  公开（公告）日：2020-02-20

  公开了通式(I)所示的靶向细胞周期依赖性激酶(CDKs)降解剂的化合物和/或其药学上可接受的盐、其药物组合物以及这些衍生物作为药物活性剂，用于预防和/或治疗CDKs异常活性相关的疾病的药物中的用途。所述化合物对实体肿瘤和血液肿瘤均具有较好的抑制细胞增殖的效果，说明具有潜在的治疗相关癌症和自身免疫性疾病的潜力。
• Is NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein–Protein Interactions?
  作者：David M. Dias、Inge Van Molle、Matthias G. J. Baud、Carles Galdeano、Carlos F. G. C. Geraldes、Alessio Ciulli

  DOI：10.1021/ml400296c

  日期：2014.1.9

  Modulation of protein-protein interactions (PPIs) with small molecules has been hampered by a lack of lucid methods capable of reliably identifying high-quality hits. In fragment screening, the low ligand efficiencies associated with PPI target sites pose significant challenges to fragment binding detection. Here, we investigate the requirements for ligand-based NMR techniques to detect rule-of-three compliant fragments that form part of known high affinity inhibitors of the PPI between the von Hippel-Lindau protein and the alpha subunit of hypoxia-inducible factor 1 (pVHL:HIF-1 alpha). Careful triaging allowed rescuing weak but specific binding of fragments that would otherwise escape detection at this PPI. Further structural information provided by saturation transfer difference (STD) group epitope mapping, protein-based NMR, competitive isothermal titration calorimetry (ITC), and X-ray crystallography confirmed the binding mode of the rescued fragments. Our findings have important implications for PPI druggability assessment by fragment screening as they reveal an accessible threshold for fragment detection and validation.