(R)-2-(2-(naphthalen-2-yloxy)acetamido)pentanedioic acid | 1092117-23-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-(2-(naphthalen-2-yloxy)acetamido)pentanedioic acid
• 英文别名: (2R)-2-[2-(naphthalen-2-yloxy)acetamido]pentanedioic acid；(2R)-2-[(2-naphthalen-2-yloxyacetyl)amino]pentanedioic acid
• CAS: 1092117-23-1
• 化学式: C₁₇H₁₇NO₆
• 分子量: 331.325
• InChiKey: JHAHLAYGYFLEHP-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (R)-dimethyl 2-(2-(naphthalen-2-yloxy)acetamido)pentanedioate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以60%的产率得到(R)-2-(2-(naphthalen-2-yloxy)acetamido)pentanedioic acid
  参考文献：
  名称：

  Novel Naphthalene-N-sulfonyl-d-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme,

  摘要：

  Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships.The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transition state analogues, displayed IC50 values ranging from 80 to 600 microM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.

  DOI：

  10.1021/jm800762u

文献信息

• Novel Naphthalene-<i>N</i>-sulfonyl-<scp>d</scp>-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme,
  作者：Jan Humljan、Miha Kotnik、Carlos Contreras-Martel、Didier Blanot、Uroš Urleb、Andréa Dessen、Tom Šolmajer、Stanislav Gobec

  DOI：10.1021/jm800762u

  日期：2008.12.11

  Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships.The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transition state analogues, displayed IC50 values ranging from 80 to 600 microM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.