5-chloro-N-(3-methoxy-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)thiophene-2-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 5-chloro-N-(3-methoxy-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)thiophene-2-sulfonamide
• 英文别名: 5-chloro-N-(3-methoxy-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)thiophene-2-sulfonamide
• 化学式: C₁₁H₁₀ClN₅O₃S₂
• 分子量: 359.817
• InChiKey: AWKFPMCWSXXRCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(dimethoxymethylidene)propanedinitrile 在 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.5h， 生成 5-chloro-N-(3-methoxy-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)thiophene-2-sulfonamide
  参考文献：
  名称：

  Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists

  摘要：

  A novel 4-aminoindazole sulfonamide hit (13) was identified as a human CCR4 antagonists from testing a focussed library of compounds in the primary GTPcS assay. Replacing the indazole core with a pyrazolopyrimidine, and introduction of a methoxy group adjacent to the sulfonamide substituent, resulted in the identification of pyrazolopyrimidine 37a, which exhibited good binding affinity in the GTPcS assay (pIC(50) = 7.2), low lipophilicity (c logP = 2.2, chromlog D-7.4 = 2.4), high LE (0.41), high solubility (CLND solubility >= 581 mu M), and an excellent PK profile in both the rat (F = 62%) and the dog (F = 100%). Further SAR investigation of the pyrazolopyrimidine suggested that substitution at N1 is tolerated, providing a suitable vector to modulate the properties, and increase the potency in a lead optimisation campaign. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.052