2-(N-formyl-N-phenylamino)-6-chloropurine | 856669-38-0

• 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: 2-(N-formyl-N-phenylamino)-6-chloropurine
• 英文别名: N-(6-chloro-7H-purin-2-yl)-N-phenylformamide
• CAS: 856669-38-0
• 化学式: C₁₂H₈ClN₅O
• 分子量: 273.681
• InChiKey: KAKYBELFIPAYCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 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：
  74.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(N-formyl-N-phenylamino)-6-chloropurine 在 sodium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 65.5h， 生成 2-anilino-9-(5-hydroxypentyl)-1H-purin-6-one
  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：

  N,N-二甲基甲酰胺 、 6-chloro-N-phenyl-9H-purin-2-amine 在 三乙胺盐酸盐 、 三氯氧磷 作用下， 反应 4.0h， 以83%的产率得到2-(N-formyl-N-phenylamino)-6-chloropurine
  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

• 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.