2-(phenylthio)hypoxanthine | 406485-11-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(phenylthio)hypoxanthine
• 英文别名: 2-Phenylsulfenylhypoxanthine；2-phenylsulfanyl-1,7-dihydropurin-6-one
• CAS: 406485-11-8
• 化学式: C₁₁H₈N₄OS
• 分子量: 244.277
• InChiKey: KLBMLVDPSMNTNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(phenylthio)hypoxanthine 在 sodium hydroxide 、 三乙胺盐酸盐 、 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 9-(4-hydroxybutyl)-2-phenylthio-6-oxopurine
  参考文献：
  名称：

  Inhibition of Herpes Simplex Virus Thymidine Kinases by 2-Phenylamino-6-oxopurines and Related Compounds:  Structure−Activity Relationships and Antiherpetic Activity in Vivo

  摘要：

  Derivatives of the herpes simplex thymidine kinase inhibitor HBPG [2-phenylamino-9-(4-hydroxybutyl)-6-oxopurine] have been synthesized and tested for inhibitory activity against recombinant enzymes (TK) from herpes simplex types 1 and 2 (HSV-1, HSV-2). The compounds inhibited phosphorylation of [H-3]thymidine by both enzymes, but potencies differed quantitatively from those of HBPG and were generally greater for HSV-2 than HSV-1 TKs. Changes in inhibitory potency were generally consistent with the inhibitor/substrate binding site structure based on published X-ray structures of HSV-1 TK. In particular, several 9-(4-aminobutyl) analogues with bulky tertiary amino substituents were among the most potent inhibitors. Variable substrate assays showed that the most potent compound, 2-phenylamino-9-[4-(1-decahydroquinolyl)butyl]-6-oxopurine, was a competitive inhibitor, with K-i values of 0.03 and 0.005 mu M against HSV-1 and HSV-2 TKs, respectively. The parent compound HBPG was uniquely active in viral infection models in mice, both against ocular HSV-2 reactivation and against HSV-1 and HSV-2 encephalitis. In assays lacking [H-3]thymidine, HBPG was found to be an efficient substrate for the enzymes. The ability of the TKs to phosphorylate HBPG may relate to its antiherpetic activity in vivo.

  DOI：

  10.1021/jm049059x
• 作为产物：
  描述：

  2-溴次黄嘌呤 、 苯硫酚 在 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 以89%的产率得到2-(phenylthio)hypoxanthine
  参考文献：
  名称：

  Methods for the synthesis of substituted purines

  摘要：

  本发明提供了一种通用方法，以组合和无痕迹的方式制备2,9-, 2,6,9-, O6-芳基-和O6-烷基取代嘌呤。在某些实施例中，该方法涉及在溶液中使用醇对2-氟-6-苯基磺酰基嘌呤的N9进行三丁基膦酸酯烷基化，随后用树脂结合胺捕获嘌呤核心的C2，然后用胺和苯胺进行C6磺酰基基团的氧化和置换。

  公开号：

  US20030171583A1

文献信息

• METHODS FOR THE SYNTHESIS OF SUBSTITUTED PURINES
  申请人：IRM LLC

  公开号：EP1529048A2

  公开（公告）日：2005-05-11
• EP1529048A4
  申请人：——

  公开号：EP1529048A4

  公开（公告）日：2005-09-14
• US6949644B2
  申请人：——

  公开号：US6949644B2

  公开（公告）日：2005-09-27
• [EN] METHODS FOR THE SYNTHESIS OF SUBSTITUTED PURINES<br/>[FR] METHODES DE SYNTHESE DE PURINES SUBSTITUEES
  申请人：IRM LLC

  公开号：WO2003031405A2

  公开（公告）日：2003-04-17

  The invention provides general methods for preparing 2,9-, 2,6,9-, O6-aryl- and O6-alkyl-substituted purines in a combinatorial and traceless fashion. The methods involve, in some embodiments, Mitsunobu alkylation of 2-fluoro-6-phenylsulfenylpurine at N9 with alcohols in solution, followed by C2-capture of the purine core with a resin-bound amine and subsequent oxidation and displacement of the C6 sulfonyl group with amines and anilines.