methyl 6-bromo-1-(N,N-dimethylsulfamoyl)-2-[(2-thienylmethyl)amino]-1H-benzimidazole-5-carboxylate | 1616350-53-8

• 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: methyl 6-bromo-1-(N,N-dimethylsulfamoyl)-2-[(2-thienylmethyl)amino]-1H-benzimidazole-5-carboxylate
• CAS: 1616350-53-8
• 化学式: C₁₆H₁₇BrN₄O₄S₂
• 分子量: 473.371
• InChiKey: GOIKEQJEMKUECG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  93.53
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl 6-bromo-1-(N,N-dimethylsulfamoyl)-2-[(2-thienylmethyl)amino]-1H-benzimidazole-5-carboxylate 、 氯甲脒盐酸盐 在 lithium hydroxide monohydrate 、 caesium carbonate 、 copper(l) iodide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.33h， 以43%的产率得到6-a mino-N,N-dimethyl-8-oxo-2-[(2-thienylmethyl)amino]-7,8-dihydro-3H-imidazo[4,5-g]quinazoline-3-sulfonamide
  参考文献：
  名称：

  Beyond Affinity: Enthalpy–Entropy Factorization Unravels Complexity of a Flat Structure–Activity Relationship for Inhibition of a tRNA-Modifying Enzyme

  摘要：

  Lead optimization focuses on binding-affinity improvement. If a flat structure activity relationship is detected, usually optimization strategies are abolished as unattractive. Nonetheless, as affinity is composed of an enthalpic and entropic contribution, factorization of both can unravel the complexity of a flat, on first sight tedious SAR. In such cases, the binding free energy of different ligands can be rather similar, but it can factorize into enthalpy and entropy distinctly. We investigated the thermodynamic signature of two classes of lin-benzopurines binding to tRNA-guanine transglycosylase. While the differences are hardly visible in the free energy, they involve striking enthalpic and entropic changes. Analyzing thermodynamics along with structural features revealed that one ligand set binds to the protein without inducing significant changes compared to the apo structure; however, the second series provokes complex adaptation, leading to a conformation similar to the substrate-bound state. In the latter state, a cross-talk between two pockets is suggested.

  DOI：

  10.1021/jm5006868
• 作为产物：
  描述：

  methyl 6-amino-1-(N,N-dimethylsulfamoyl)-2-[(2-thienylmethyl)amino]-1H-benzimidazole-5-carboxylate 在 氢溴酸 、 溶剂黄146 、 sodium nitrite 、 copper(I) bromide 作用下， 以 水 为溶剂， 反应 2.0h， 以30%的产率得到methyl 6-bromo-1-(N,N-dimethylsulfamoyl)-2-[(2-thienylmethyl)amino]-1H-benzimidazole-5-carboxylate
  参考文献：
  名称：

  Beyond Affinity: Enthalpy–Entropy Factorization Unravels Complexity of a Flat Structure–Activity Relationship for Inhibition of a tRNA-Modifying Enzyme

  摘要：

  Lead optimization focuses on binding-affinity improvement. If a flat structure activity relationship is detected, usually optimization strategies are abolished as unattractive. Nonetheless, as affinity is composed of an enthalpic and entropic contribution, factorization of both can unravel the complexity of a flat, on first sight tedious SAR. In such cases, the binding free energy of different ligands can be rather similar, but it can factorize into enthalpy and entropy distinctly. We investigated the thermodynamic signature of two classes of lin-benzopurines binding to tRNA-guanine transglycosylase. While the differences are hardly visible in the free energy, they involve striking enthalpic and entropic changes. Analyzing thermodynamics along with structural features revealed that one ligand set binds to the protein without inducing significant changes compared to the apo structure; however, the second series provokes complex adaptation, leading to a conformation similar to the substrate-bound state. In the latter state, a cross-talk between two pockets is suggested.

  DOI：

  10.1021/jm5006868