2-Phenylsulfenyl-6-chloro-purine | 406485-12-9

• 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-Phenylsulfenyl-6-chloro-purine
• 英文别名: 6-chloro-2-phenylsulfanyl-7H-purine
• CAS: 406485-12-9
• 化学式: C₁₁H₇ClN₄S
• 分子量: 262.722
• InChiKey: AIWRSQAAWQUHFT-UHFFFAOYSA-N

物化性质

• 沸点：
  594.9±53.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 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：
  79.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Phenylsulfenyl-6-chloro-purine 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  9-(4-[18F] 氟-3-(羟甲基)丁基)-2-(苯硫基)-6-氧嘌呤作为突变型单纯疱疹病毒 1 型胸苷激酶报告基因成像的新型 PET 试剂的合成和表征。

  摘要：

  目的[ 18 F] FHBG 已被用作正电子发射断层扫描 (PET) 成像示踪剂，用于监测单纯疱疹病毒 1 型胸苷激酶 (HSV1-tk)，这是一种用于人类细胞和基因治疗的报告基因。然而，这种示踪剂显示血脑屏障 (BBB) 渗透不足，因此，对于大脑中报告基因表达的准确量化将受到限制。在这里，我们报告了 9-(4-[ 18 F] 氟-3-(羟甲基)丁基)-2(苯硫基)-6-氧嘌呤 ([ 18 F]FHBT) 作为一种新的 PET 成像示踪剂的合成和评估HSV1-tk 及其突变体 HSV1-sr39tk 的报告基因表达，目的是提高 BBB 渗透率。 程序[ 18 F]FHBT是通过使用甲苯磺酸盐前体和[ 18 F]KF制备的。[ 18 F]FHBT的细胞摄取在HSV1-sr39tk-阳性(+)或HSV1-sr39tk-阴性(-)MDA-MB-231乳腺癌细胞中进行。[ 18 F]FHBT 评估

  DOI：

  10.1007/s11307-020-01517-5
• 作为产物：
  描述：

  2-溴次黄嘌呤 在 三乙胺盐酸盐 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2-Phenylsulfenyl-6-chloro-purine
  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

文献信息

• Methods for the synthesis of substituted purines
  申请人：IRM LLC, a Delaware Limited Liability Company

  公开号：US20030171583A1

  公开（公告）日：2003-09-11

  The invention provides general methods for preparing 2,9-, 2,6,9-, O 6 -aryl- and O 6 -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.

  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。
• US6949644B2
  申请人：——

  公开号：US6949644B2

  公开（公告）日：2005-09-27
• Inhibition of Herpes Simplex Virus Thymidine Kinases by 2-Phenylamino-6-oxopurines and Related Compounds:  Structure−Activity Relationships and Antiherpetic Activity in Vivo
  作者：Andrzej Manikowski、Annalisa Verri、Andrea Lossani、Bryan M. Gebhardt、Joseph Gambino、Federico Focher、Silvio Spadari、George E. Wright

  DOI：10.1021/jm049059x

  日期：2005.6.1

  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.
• Synthesis and Characterization of 9-(4-[18F]Fluoro-3-(hydroxymethyl)butyl)-2-(phenylthio)-6-oxopurine as a Novel PET Agent for Mutant Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Imaging
  作者：Takeshi Fuchigami、Tom Haywood、Gayatri Gowrishankar、David Anders、Mohammad Namavari、Mirwais Wardak、Sanjiv Sam Gambhir

  DOI：10.1007/s11307-020-01517-5

  日期：2020.10

  Here, we report the synthesis and evaluation of 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)-2(phenylthio)-6-oxopurine ([18F]FHBT) as a new PET tracer for imaging reporter gene expression of HSV1-tk and its mutant HSV1-sr39tk, with the aim of improved BBB penetration. Procedures[18F]FHBT was prepared by using a tosylate precursor and [18F]KF. The cellular uptake of [18F]FHBT was performed in HSV1-sr39tk-positive

  目的[ 18 F] FHBG 已被用作正电子发射断层扫描 (PET) 成像示踪剂，用于监测单纯疱疹病毒 1 型胸苷激酶 (HSV1-tk)，这是一种用于人类细胞和基因治疗的报告基因。然而，这种示踪剂显示血脑屏障 (BBB) 渗透不足，因此，对于大脑中报告基因表达的准确量化将受到限制。在这里，我们报告了 9-(4-[ 18 F] 氟-3-(羟甲基)丁基)-2(苯硫基)-6-氧嘌呤 ([ 18 F]FHBT) 作为一种新的 PET 成像示踪剂的合成和评估HSV1-tk 及其突变体 HSV1-sr39tk 的报告基因表达，目的是提高 BBB 渗透率。 程序[ 18 F]FHBT是通过使用甲苯磺酸盐前体和[ 18 F]KF制备的。[ 18 F]FHBT的细胞摄取在HSV1-sr39tk-阳性(+)或HSV1-sr39tk-阴性(-)MDA-MB-231乳腺癌细胞中进行。[ 18 F]FHBT 评估