3-(2-amino-6-(cyclohexylmethoxy)-9H-purin-8-yl)-2-methylbenzenesulfonamide | 1520101-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-amino-6-(cyclohexylmethoxy)-9H-purin-8-yl)-2-methylbenzenesulfonamide
• 英文别名: 3-[2-Amino-6-(Cyclohexylmethoxy)-7h-Purin-8-Yl]-2-Methylbenzenesulfonamide；3-[2-amino-6-(cyclohexylmethoxy)-7H-purin-8-yl]-2-methylbenzenesulfonamide
• CAS: 1520101-60-3
• 化学式: C₁₉H₂₄N₆O₃S
• 分子量: 416.504
• InChiKey: MTASIWVJZCLGMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(2-amino-6-(cyclohexylmethoxy)-9H-purin-8-yl)-N,N-bis(4-methoxybenzyl)-2-methylbenzenesulfonamide 在 三氟乙酸 作用下， 反应 1.5h， 以78%的产率得到3-(2-amino-6-(cyclohexylmethoxy)-9H-purin-8-yl)-2-methylbenzenesulfonamide
  参考文献：
  名称：

  8-Substituted O⁶-Cyclohexylmethylguanine CDK2 Inhibitors: Using Structure-Based Inhibitor Design to Optimize an Alternative Binding Mode

  摘要：

  Evaluation of the effects of purine C-8 substitution within a series of CDK1/2-selective O-6-cyclohexylmethylguanine derivatives revealed that potency decreases initially with increasing size of the alkyl substituent. Structural analysis showed that C-8 substitution is poorly tolerated, and to avoid unacceptable steric interactions, these compounds adopt novel binding modes. Thus, 2-amino-6-cyclohexylmethoxy-8-isopropyl-9H-purine adopts a "reverse" binding mode where the purine backbone has flipped 180 degrees. This provided a novel lead chemotype from which we have designed more potent CDK2 inhibitors using, in the first instance, quantum mechanical energy calculations. Introduction of an ortho-tolyl or ortho-chlorophenyl group at the purine C-8 position restored the potency of these "reverse" binding mode inhibitors to that of the parent 2-amino-6-cyclohexylmethoxy-9H-purine. By contrast, the corresponding 8-(2-methyl-3-sulfamoylphenyl)-purine derivative exhibited submicromolar CDK2-inhibitory activity by virtue of engineered additional interactions with Asp86 and Lys89 in the reversed binding mode, as confirmed by X-ray crystallography.

  DOI：

  10.1021/jm401555v