(N-[3-(2-chloro-phenylcarbamoyl)-propionyl]-hydrazino)acetic acid | 1236049-84-5

• 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: (N-[3-(2-chloro-phenylcarbamoyl)-propionyl]-hydrazino)acetic acid
• 英文别名: 2-[Amino-[4-(2-chloroanilino)-4-oxobutanoyl]amino]acetic acid
• CAS: 1236049-84-5
• 化学式: C₁₂H₁₄ClN₃O₄
• 分子量: 299.714
• InChiKey: OFGMKCPRGWVYLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (N-[3-(2-chloro-phenylcarbamoyl)-propionyl]-hydrazino)acetic acid 、 1-萘甲醛 以 乙醇 为溶剂， 反应 12.0h， 以47%的产率得到(N-[3-(2-chloro-phenylcarbamoyl)-propionyl]-N'-naphthalen-1-ylmethylene-hydrazino)acetic acid
  参考文献：
  名称：

  Complexes of Bacterial Nicotinate Mononucleotide Adenylyltransferase with Inhibitors: Implication for Structure-Based Drug Design and Improvement

  摘要：

  Bacterial nicotinate mononucleotide adenylyltransferase encoded by the essential gene nadD plays a central role in the synthesis of the redox cofactor NAD(+). The NadD enzyme is conserved in the majority of bacterial species and has been recognized as a novel target for developing new and potentially broad-spectrum antibacterial therapeutics. Here we report the crystal structures of Bacillus anthracis NadD in complex with three NadD inhibitors, including two analogues synthesized in the present study. These structures revealed a common binding site shared by different classes of NadD inhibitors and explored the chemical environment surrounding this site. The structural data obtained here also showed that the subtle changes in ligand structure can lead to significant changes in the binding mode, information that will be useful for future structure-based optimization and design of high affinity inhibitors.

  DOI：

  10.1021/jm100377f
• 作为产物：
  描述：

  4-(N'-tert-butoxycarbonyl-N-ethoxycarbonylmethylhydrazino)-4-oxo-butyric acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 (N-[3-(2-chloro-phenylcarbamoyl)-propionyl]-hydrazino)acetic acid
  参考文献：
  名称：

  [EN] TARGETING NAD BIOSYNTHESIS IN BACTERIAL PATHOGENS
  [FR] CIBLAGE DE LA BIOSYNTHÈSE DE LA NAD DANS DES BACTÉRIES PATHOGÈNES

  摘要：

  公开号：

  WO2011006158A3

文献信息

• TARGETING NAD BIOSYNTHESIS IN BACTERIAL PATHOGENS
  申请人：Mackerell, JR. Alexander

  公开号：US20120190708A1

  公开（公告）日：2012-07-26

  The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. To this end, the inventors have identified small molecule compounds that inhibit bacterial target enzymes by interacting with a novel inhibitory binding site on the enzyme while having no effect on functionally equivalent human enzymes.

  多重耐药病原体的出现需要寻找作用于先前未被开发的靶标的新抗生素。Nicotinate单核苷酸腺苷转移酶（NadD家族），是大多数细菌NAD生物合成的必需酶，被选为基于结构的抑制剂开发的目标。为此，发明人已经鉴定出小分子化合物，通过与酶上的新型抑制性结合位点相互作用来抑制细菌靶标酶，而对功能相当的人类酶没有影响。
• US8785499B2
  申请人：——

  公开号：US8785499B2

  公开（公告）日：2014-07-22
• Complexes of Bacterial Nicotinate Mononucleotide Adenylyltransferase with Inhibitors: Implication for Structure-Based Drug Design and Improvement
  作者：Nian Huang、Rohit Kolhatkar、Yvonne Eyobo、Leonardo Sorci、Irina Rodionova、Andrei L. Osterman、Alexander D. MacKerell、Hong Zhang

  DOI：10.1021/jm100377f

  日期：2010.7.22

  Bacterial nicotinate mononucleotide adenylyltransferase encoded by the essential gene nadD plays a central role in the synthesis of the redox cofactor NAD(+). The NadD enzyme is conserved in the majority of bacterial species and has been recognized as a novel target for developing new and potentially broad-spectrum antibacterial therapeutics. Here we report the crystal structures of Bacillus anthracis NadD in complex with three NadD inhibitors, including two analogues synthesized in the present study. These structures revealed a common binding site shared by different classes of NadD inhibitors and explored the chemical environment surrounding this site. The structural data obtained here also showed that the subtle changes in ligand structure can lead to significant changes in the binding mode, information that will be useful for future structure-based optimization and design of high affinity inhibitors.
• [EN] TARGETING NAD BIOSYNTHESIS IN BACTERIAL PATHOGENS<br/>[FR] CIBLAGE DE LA BIOSYNTHÈSE DE LA NAD DANS DES BACTÉRIES PATHOGÈNES
  申请人：UNIV MARYLAND

  公开号：WO2011006158A3

  公开（公告）日：2011-05-19