5'-azido-8-carboxymethylthio-5'-deoxyadenosine | 1383460-48-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-azido-8-carboxymethylthio-5'-deoxyadenosine
• 英文别名: 8-Carboxymethylthio-5'-azido-5'-deoxyadenosine；2-[6-amino-9-[(2R,3R,4S,5R)-5-(azidomethyl)-3,4-dihydroxyoxolan-2-yl]purin-8-yl]sulfanylacetic acid
• CAS: 1383460-48-7
• 化学式: C₁₂H₁₄N₈O₅S
• 分子量: 382.36
• InChiKey: ZAAKCPNKOSZGPF-TZQXKBMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  196
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  5'-azido-8-carboxymethylthio-5'-deoxyadenosine 生成
  参考文献：
  名称：

  Screening and In Situ Synthesis Using Crystals of a NAD Kinase Lead to a Potent Antistaphylococcal Compound

  摘要：

  Making new ligands for a given protein by in situ ligation of building blocks (or fragments) is an attractive method. However, it suffers from inherent limitations, such as the limited number of available chemical reactions and the low information content of usual chemical library deconvolution. Here, we describe a focused screening of adenosine derivatives using X-ray crystallography. We discovered an unexpected and biocompatible chemical reactivity and have simultaneously identified the mode of binding of the resulting products. We observed that the NAD kinase from Listeria monocytogenes (LmNADK1) can promote amide formation between 5'-amino-5'-deoxyadenosine and carboxylic acid groups. This unexpected reactivity allowed us to bridge in situ two adenosine derivatives to fully occupy the active NAD site. This guided the design of a close analog showing micromolar inhibition of two human pathogenic NAD kinases and potent bactericidal activity against Staphylococcus aureus in vitro.

  DOI：

  10.1016/j.str.2012.03.024
• 作为产物：
  描述：

  5'-azido-5'-deoxyadenosine 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5'-azido-8-carboxymethylthio-5'-deoxyadenosine
  参考文献：
  名称：

  Screening and In Situ Synthesis Using Crystals of a NAD Kinase Lead to a Potent Antistaphylococcal Compound

  摘要：

  Making new ligands for a given protein by in situ ligation of building blocks (or fragments) is an attractive method. However, it suffers from inherent limitations, such as the limited number of available chemical reactions and the low information content of usual chemical library deconvolution. Here, we describe a focused screening of adenosine derivatives using X-ray crystallography. We discovered an unexpected and biocompatible chemical reactivity and have simultaneously identified the mode of binding of the resulting products. We observed that the NAD kinase from Listeria monocytogenes (LmNADK1) can promote amide formation between 5'-amino-5'-deoxyadenosine and carboxylic acid groups. This unexpected reactivity allowed us to bridge in situ two adenosine derivatives to fully occupy the active NAD site. This guided the design of a close analog showing micromolar inhibition of two human pathogenic NAD kinases and potent bactericidal activity against Staphylococcus aureus in vitro.

  DOI：

  10.1016/j.str.2012.03.024

文献信息

• [EN] NOVEL ANTIBACTERIAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS ANTIBACTÉRIENS
  申请人：PASTEUR INSTITUT

  公开号：WO2012090136A1

  公开（公告）日：2012-07-05

  The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim 1. The compounds are useful in the prevention and/or treatment of bacterial infections.

  本发明涉及以下化合物的公式(I)：其中R1、R2、R3、R4、X1、X2、X3和Z的定义如权利要求1所述。这些化合物在预防和/或治疗细菌感染方面具有用途。
• NOVEL ANTIBACTERIAL COMPOUNDS
  申请人：Pochet Sylvie

  公开号：US20130331351A1

  公开（公告）日：2013-12-12

  The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim 1 . The compounds are useful in the prevention and/or treatment of bacterial infections.

  本发明涉及公式（I）的化合物：其中Rj，R2，R3，R4，Xi，X2，X3和Z如权利要求1所定义。该化合物对于预防和/或治疗细菌感染有用。
• Antibacterial compounds
  申请人：Pochet Sylvie

  公开号：US08927520B2

  公开（公告）日：2015-01-06

  The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim 1. The compounds are useful in the prevention and/or treatment of bacterial infections.

  本发明涉及式(I)的化合物：其中Rj、R2、R3、R4、Xi、X2、X3和Z如权利要求1所定义。该化合物在预防和/或治疗细菌感染方面具有用途。
• Diadenosine antibacterial compounds
  申请人：Institut Pasteur

  公开号：EP2471804B1

  公开（公告）日：2013-11-06
• US8927520B2
  申请人：——

  公开号：US8927520B2

  公开（公告）日：2015-01-06