6-Amino-1-Benzyl-5-(Ethylamino)pyrimidine-2,4(1h,3h)-Dione | 565193-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-Amino-1-Benzyl-5-(Ethylamino)pyrimidine-2,4(1h,3h)-Dione
• 英文别名: 6-amino-1-benzyl-5-(ethylamino)pyrimidine-2,4-dione
• CAS: 565193-15-9
• 化学式: C₁₃H₁₆N₄O₂
• mdl: MFCD03966870
• 分子量: 260.296
• InChiKey: DHIDSSFRXLUFLN-UHFFFAOYSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  87.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-Amino-1-Benzyl-5-(Ethylamino)pyrimidine-2,4(1h,3h)-Dione 、 苯磺酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以54%的产率得到N-(6-amino-1-benzyl-2,4-dioxopyrimidin-5-yl)-N-ethylbenzenesulfonamide
  参考文献：
  名称：

  Allosteric Competitive Inhibitors of the Glucose-1-phosphate Thymidylyltransferase (RmlA) from Pseudomonas aeruginosa

  摘要：

  Glucose-1-phosphate thymidylyltransferase (RmlA) catalyzes the condensation of glucose-1-phosphate (G1P) with deoxy-thymidine triphosphate (dTTP) to yield dTDP-D-glucose and pyrophosphate. This is the first step in the L-rhamnose biosynthetic pathway. L-Rhamnose is an important component of the cell wall of many microorganisms, including Mycobacterium tuberculosis and Pseudomonas aeruginosa. Here we describe the first nanomolar inhibitors of P. aeruginosa RmlA. These thymine analogues were identified by high-throughput screening and subsequently optimized by a combination of protein crystallography, in silico screening, and synthetic chemistry. Some of the inhibitors show inhibitory activity against M. tuberculosis, The inhibitors do not bind at the active site of RmlA but bind at a second site active site. Despite this, the compounds act as competitive inhibitors of G1P but with high cooperativity. This novel behavior was probed by structural analysis, which suggests that the inhibitors work by preventing RmlA from undergoing the conformational change key to its ordered bi-bi mechanism.

  DOI：

  10.1021/cb300426u
• 作为产物：
  描述：

  苄脲 在 溴 、 乙酸酐 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 7.5h， 生成 6-Amino-1-Benzyl-5-(Ethylamino)pyrimidine-2,4(1h,3h)-Dione
  参考文献：
  名称：

  Allosteric Competitive Inhibitors of the Glucose-1-phosphate Thymidylyltransferase (RmlA) from Pseudomonas aeruginosa

  摘要：

  Glucose-1-phosphate thymidylyltransferase (RmlA) catalyzes the condensation of glucose-1-phosphate (G1P) with deoxy-thymidine triphosphate (dTTP) to yield dTDP-D-glucose and pyrophosphate. This is the first step in the L-rhamnose biosynthetic pathway. L-Rhamnose is an important component of the cell wall of many microorganisms, including Mycobacterium tuberculosis and Pseudomonas aeruginosa. Here we describe the first nanomolar inhibitors of P. aeruginosa RmlA. These thymine analogues were identified by high-throughput screening and subsequently optimized by a combination of protein crystallography, in silico screening, and synthetic chemistry. Some of the inhibitors show inhibitory activity against M. tuberculosis, The inhibitors do not bind at the active site of RmlA but bind at a second site active site. Despite this, the compounds act as competitive inhibitors of G1P but with high cooperativity. This novel behavior was probed by structural analysis, which suggests that the inhibitors work by preventing RmlA from undergoing the conformational change key to its ordered bi-bi mechanism.

  DOI：

  10.1021/cb300426u

文献信息

• Allosteric Competitive Inhibitors of the Glucose-1-phosphate Thymidylyltransferase (RmlA) from <i>Pseudomonas aeruginosa</i>
  作者：Magnus S. Alphey、Lisa Pirrie、Leah S. Torrie、Wassila Abdelli Boulkeroua、Mary Gardiner、Aurijit Sarkar、Marko Maringer、Wulf Oehlmann、Ruth Brenk、Michael S. Scherman、Michael McNeil、Martin Rejzek、Robert A. Field、Mahavir Singh、David Gray、Nicholas J. Westwood、James H. Naismith

  DOI：10.1021/cb300426u

  日期：2013.2.15

  Glucose-1-phosphate thymidylyltransferase (RmlA) catalyzes the condensation of glucose-1-phosphate (G1P) with deoxy-thymidine triphosphate (dTTP) to yield dTDP-D-glucose and pyrophosphate. This is the first step in the L-rhamnose biosynthetic pathway. L-Rhamnose is an important component of the cell wall of many microorganisms, including Mycobacterium tuberculosis and Pseudomonas aeruginosa. Here we describe the first nanomolar inhibitors of P. aeruginosa RmlA. These thymine analogues were identified by high-throughput screening and subsequently optimized by a combination of protein crystallography, in silico screening, and synthetic chemistry. Some of the inhibitors show inhibitory activity against M. tuberculosis, The inhibitors do not bind at the active site of RmlA but bind at a second site active site. Despite this, the compounds act as competitive inhibitors of G1P but with high cooperativity. This novel behavior was probed by structural analysis, which suggests that the inhibitors work by preventing RmlA from undergoing the conformational change key to its ordered bi-bi mechanism.