8-(Acetylmethylthio)guanin | 51011-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-(Acetylmethylthio)guanin
• 英文别名: 2-amino-8-(2-oxo-propylsulfanyl)-1,7(9)-dihydro-purin-6-one；2-Amino-8-(2-oxopropylsulfanyl)-1,7-dihydropurin-6-one；2-amino-8-(2-oxopropylsulfanyl)-1,7-dihydropurin-6-one
• CAS: 51011-85-9
• 化学式: C₈H₉N₅O₂S
• 分子量: 239.258
• InChiKey: CPDNFQMNPGNUMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(Acetylmethylthio)guanin 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 2-Amino-4-hydroxy-6-methylthiazolo<2,3-f>purin
  参考文献：
  名称：

  Syntheses of thiazolo(2,3-f)guaninederivatives.

  摘要：

  Thiazolo [2, 3-f] guanines were synthesized by the cyclization of 8-acylmethylthioguanines. Structure of these compounds were determined by desulfurization with Raney Ni.

  DOI：

  10.1248/cpb.23.450
• 作为产物：
  描述：

  8-mercaptoguanine 、 一氯丙酮 生成 8-(Acetylmethylthio)guanin
  参考文献：
  名称：

  UNO H.; IRIE A.; HINO K., CHEM. AND PHARM. BULL. , 1975, 23, NO 2, 450-451

  摘要：

  DOI：

文献信息

• Structure-Based Design and Development of Functionalized Mercaptoguanine Derivatives as Inhibitors of the Folate Biosynthesis Pathway Enzyme 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from <i>Staphylococcus aureus</i>
  作者：Matthew L. Dennis、Sandeep Chhabra、Zhong-Chang Wang、Aaron Debono、Olan Dolezal、Janet Newman、Noel P. Pitcher、Raphael Rahmani、Ben Cleary、Nicholas Barlow、Meghan Hattarki、Bim Graham、Thomas S. Peat、Jonathan B. Baell、James D. Swarbrick

  DOI：10.1021/jm501417f

  日期：2014.11.26

  6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), an enzyme from the folate biosynthesis pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin and is a yet-to-be-drugged antimicrobial target. Building on our previous discovery that 8-mercaptoguanine (8MG) is an inhibitor of Staphylococcus aureus HPPK (SaHPPK), we have identified and characterized the binding of an S8-functionalized derivative (3). X-ray structures of both the SaHPPK/3/cofactor analogue ternary and the SaHPPK/cofactor analogue binary complexes have provided insight into cofactor recognition and key residues that move over 30 angstrom upon binding of 3, whereas NMR measurements reveal a partially plastic ternary complex active site. Synthesis and binding analysis of a set of analogues of 3 have identified an advanced new lead compound (11) displaying >20-fold higher affinity for SaHPPK than 8MG. A number of these exhibited low micromolar affinity for dihydropteroate synthase (DHPS), the adjacent, downstream enzyme to HPPK, and may thus represent promising new leads to bienzyme inhibitors.