2,3-dichloro-N-(3-(2-methoxyethoxy)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)benzenesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,3-dichloro-N-(3-(2-methoxyethoxy)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)benzenesulfonamide
• 英文别名: 2,3-dichloro-N-[3-(2-methoxyethoxy)-1-methylpyrazolo[3,4-d]pyrimidin-4-yl]benzenesulfonamide
• 化学式: C₁₅H₁₅Cl₂N₅O₄S
• 分子量: 432.287
• InChiKey: AFZZAPRHJGPRBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-amino-3-(2-methoxyethoxy)-1-methyl-1H-pyrazole-4-carbonitrile 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 生成 2,3-dichloro-N-(3-(2-methoxyethoxy)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)benzenesulfonamide
  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

文献信息

• Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists
  作者：Afjal H. Miah、Aurelie C. Champigny、Rebecca H. Graves、Simon T. Hodgson、Jonathan M. Percy、Panayiotis A. Procopiou

  DOI：10.1016/j.bmc.2017.07.052

  日期：2017.10

  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.