5-(2,3-difluoro-phenylsulfanylmethyl)-3-cyano-pyrazolo[1,5-a]pyrimidin-7-ol | 1028842-21-8

• 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-(2,3-difluoro-phenylsulfanylmethyl)-3-cyano-pyrazolo[1,5-a]pyrimidin-7-ol
• CAS: 1028842-21-8
• 化学式: C₁₄H₈F₂N₄OS
• 分子量: 318.307
• InChiKey: GXGFWSFOHDNNHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.21
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2,3-二氟苯酚 在 三乙烯二胺 、 dowtherm A 、 sodium methylate 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 5-(2,3-difluoro-phenylsulfanylmethyl)-3-cyano-pyrazolo[1,5-a]pyrimidin-7-ol
  参考文献：
  名称：

  The discovery of potent, orally bioavailable pyrazolo and triazolopyrimidine CXCR2 receptor antagonists

  摘要：

  A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrazolopyrimidine 2-methyl-5-((phenylthio)methyl)pyrazolo[1,5-a]pyrimidin-7-ol 1, resulting in the discovery of CXCR2 receptor antagonist 2-benzyl-5-(((2,3-difluorophenyl)thio)methyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol 14. The SAR was investigated by systematic variation of the pendant thiol, alkyl and pyrimidinol groups. Replacement of the pyrazolopyrimidine core with a triazolo alternative led to a dual series of antagonists with favourable biological and pharmacokinetic properties. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.074

文献信息

• CXCR2 INHIBITORS
  申请人：Hunt Peter

  公开号：US20100152205A1

  公开（公告）日：2010-06-17

  The present invention relates to compounds of formula (I) and the use of these compounds as pharmaceuticals, e.g. in preventing or treating a CXCR2 receptor mediated condition or disease.

  本发明涉及式（I）的化合物以及将这些化合物用作药物的用途，例如在预防或治疗CXCR2受体介导的疾病或疾病中。
• 5-SULFANYLMETHYL-PYRAZOLO [1,5-A]PYRIMIDIN-7-OL DERIVATIVES AS CXCR2 ANTAGONISTS
  申请人：NOVARTIS AG

  公开号：EP2094697A1

  公开（公告）日：2009-09-02
• [EN] 5-SULFANYLMETHYL-PYRAZOLO [1,5-A] PYRIMIDIN-7-OL DERIVATIVES AS CXCR2 ANTAGONISTS<br/>[FR] DERIVES DE 5-SULFANYLMETHYL-PYRAZOLO[1,5-A]PYRIMIDIN-7-OL UTILISES EN TANT QU'ANTAGONISTES DU CXCR2
  申请人：NOVARTIS AG

  公开号：WO2008062026A1

  公开（公告）日：2008-05-29

  [EN] The present invention relates to compounds of formula (I) and the use of these compounds as pharmaceuticals, e.g. in preventing or treating a CXCR2 receptor mediated condition or disease.
  [FR] L'invention concerne des composés de formule (I), ainsi que l'utilisation de ces composés comme médicaments, par exemple dans la prévention ou le traitement d'une affection ou d'une maladie induite par le récepteur CXCR2.
• The discovery of potent, orally bioavailable pyrazolo and triazolopyrimidine CXCR2 receptor antagonists
  作者：David W. Porter、Michelle Bradley、Zarin Brown、Riccardo Canova、Steven Charlton、Brian Cox、Peter Hunt、David Kolarik、Sarah Lewis、Des O’Connor、John Reilly、Carsten Spanka、Lauren Tedaldi、Simon J. Watson、Roland Wermuth、Neil J. Press

  DOI：10.1016/j.bmcl.2013.11.074

  日期：2014.1

  A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrazolopyrimidine 2-methyl-5-((phenylthio)methyl)pyrazolo[1,5-a]pyrimidin-7-ol 1, resulting in the discovery of CXCR2 receptor antagonist 2-benzyl-5-(((2,3-difluorophenyl)thio)methyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol 14. The SAR was investigated by systematic variation of the pendant thiol, alkyl and pyrimidinol groups. Replacement of the pyrazolopyrimidine core with a triazolo alternative led to a dual series of antagonists with favourable biological and pharmacokinetic properties. (C) 2013 Elsevier Ltd. All rights reserved.