(1S,2S)-2-[5-cyano-2-(2,3-difluorobenzylsulfanyl)-6hydroxy-pyrimidin-4-yl]cyclopropanecarboxylic acid | 1029521-50-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (1S,2S)-2-[5-cyano-2-(2,3-difluorobenzylsulfanyl)-6hydroxy-pyrimidin-4-yl]cyclopropanecarboxylic acid
• 英文别名: (1S,2S)-2-[5-cyano-2-[(2,3-difluorophenyl)methylsulfanyl]-6-oxo-1H-pyrimidin-4-yl]cyclopropane-1-carboxylic acid
• CAS: 1029521-50-3
• 化学式: C₁₆H₁₁F₂N₃O₃S
• 分子量: 363.344
• InChiKey: CGWUSHFJEIHQNC-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,2S)-2-[5-cyano-2-(2,3-difluorobenzylsulfanyl)-6hydroxy-pyrimidin-4-yl]cyclopropanecarboxylic acid 在 diborane(6) 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 以51%的产率得到2-(1S,2S)-2-(2,3-difluorobenzylsulfanyl)-4-hydroxy-6-(2-hydroxymethyl-cyclopropyl)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists

  摘要：

  A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrimidine 2-((2,6-dichlorobenzyl)thio)-5-isocyano-6-phenylpyrimidin-4-ol 4, resulting in the discovery of CXCR2 receptor antagonist 24(2,3-difluorobenzyl)thio)-6-(2-(hydroxymethyl)cyclopropyl)-5-isocyanopyrimidin-4-ol 24. The SAR was investigated by systematic variation of the aromatic group at c-6, the linker between c-2 and the halogenated ring, and the c-5 nitrile moiety. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.011
• 作为产物：
  描述：

  Trans-2-[5-cyano-2-(2,3-difluoro-benzylsulfanyl)-6-hydroxy-pyrimidin-4-yl]-cyclopropanecarboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以83%的产率得到(1S,2S)-2-[5-cyano-2-(2,3-difluorobenzylsulfanyl)-6hydroxy-pyrimidin-4-yl]cyclopropanecarboxylic acid
  参考文献：
  名称：

  The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists

  摘要：

  A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrimidine 2-((2,6-dichlorobenzyl)thio)-5-isocyano-6-phenylpyrimidin-4-ol 4, resulting in the discovery of CXCR2 receptor antagonist 24(2,3-difluorobenzyl)thio)-6-(2-(hydroxymethyl)cyclopropyl)-5-isocyanopyrimidin-4-ol 24. The SAR was investigated by systematic variation of the aromatic group at c-6, the linker between c-2 and the halogenated ring, and the c-5 nitrile moiety. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.011

文献信息

• CXCR2 inhibitors
  申请人：Press Neil John

  公开号：US20100063080A1

  公开（公告）日：2010-03-11

  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.

  本发明涉及公式(I)的化合物以及这些化合物作为药物的使用，例如在预防或治疗CXCR2受体介导的疾病或病症方面的使用。
• WO2008/61740
  申请人：——

  公开号：——

  公开（公告）日：——