6-amino-2-[(2-thienylmethyl)amino]-1,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one | 1001242-79-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-amino-2-[(2-thienylmethyl)amino]-1,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one
• 英文别名: 6-Amino-2-[(Thiophen-2-Ylmethyl)amino]-1,7-Dihydro-8h-Imidazo[4,5-G]quinazolin-8-One；6-amino-2-(thiophen-2-ylmethylamino)-1,7-dihydroimidazo[4,5-g]quinazolin-8-one
• CAS: 1001242-79-0
• 化学式: C₁₄H₁₂N₆OS
• 分子量: 312.355
• InChiKey: IQKMJWDYMFWZRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 6-amino-1-(N,N-dimethylsulfamoyl)-2-[(2-thienylmethyl)amino]-1H-benzimidazole-5-carboxylate 在 盐酸 、 lithium hydroxide monohydrate 、 氢溴酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 甲醇 、 水 为溶剂， 反应 25.83h， 生成 6-amino-2-[(2-thienylmethyl)amino]-1,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one
  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

文献信息

• Potent Inhibitors of tRNA-Guanine Transglycosylase, an Enzyme Linked to the Pathogenicity of theShigella Bacterium: Charge-Assisted Hydrogen Bonding
  作者：Simone R. Hörtner、Tina Ritschel、Bernhard Stengl、Christian Kramer、W. Bernd Schweizer、Björn Wagner、Manfred Kansy、Gerhard Klebe、François Diederich

  DOI：10.1002/anie.200702961

  日期：2007.11.5
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• Beyond Affinity: Enthalpy–Entropy Factorization Unravels Complexity of a Flat Structure–Activity Relationship for Inhibition of a tRNA-Modifying Enzyme
  作者：Manuel Neeb、Michael Betz、Andreas Heine、Luzi Jakob Barandun、Christoph Hohn、François Diederich、Gerhard Klebe

  DOI：10.1021/jm5006868

  日期：2014.7.10

  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.