5-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5-ethynyl-pyrimidin-2-yl)thiophene-2-sulfonamide | 1266477-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5-ethynyl-pyrimidin-2-yl)thiophene-2-sulfonamide
• 英文别名: 5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-ethynylpyrimidin-2-yl)thiophene-2-sulfonamide；5-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-ethynylpyrimidin-2-yl]thiophene-2-sulfonamide
• CAS: 1266477-79-5
• 化学式: C₁₆H₁₄N₆O₂S₂
• 分子量: 386.458
• InChiKey: QIPVDTXIJXIZGR-UHFFFAOYSA-N

物化性质

• 沸点：
  604.7±65.0 °C(Predicted)
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5-ethynyl-pyrimidin-2-yl)thiophene-2-sulfonamide 在 4-二甲氨基吡啶 、 乙醇 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-[[5-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-ethynyl-pyrimidin-2-yl]-2-thienyl]sulfonyl]acetamide
  参考文献：
  名称：

  [EN] PYRIMIDINE COMPOUNDS AS TUBERCULOSIS INHIBITORS
  [FR] COMPOSÉS PYRIMIDINE EN TANT QU'INHIBITEURS DE LA TUBERCULOSE

  摘要：

  本发明涉及化合物II，用作治疗结核病的抑制剂。该发明还提供了制备本发明化合物的方法。

  公开号：

  WO2011019405A1
• 作为产物：
  描述：

  N-(tert-butyl)-5-(4-((3-cyclopropyl-1H-pyrazol-5-yl)amino)-5-ethynylpyrimidin-2-yl)thiophene-2-sulfonamide 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以44.8%的产率得到5-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5-ethynyl-pyrimidin-2-yl)thiophene-2-sulfonamide
  参考文献：
  名称：

  Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions

  摘要：

  Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (K-i approximate to 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 mu M (1-2 mu g/mL) against the H37Ra isolate of M. tuberculosis.

  DOI：

  10.1021/acsmedchemlett.7b00239

文献信息

• PYRIMIDINE COMPOUNDS AS TUBERCULOSIS INHIBITORS
  申请人：Wang Tiansheng

  公开号：US20110053916A1

  公开（公告）日：2011-03-03

  The present invention relates to compounds useful as inhibitors of treating tuberculosis. The invention also provides processes for preparing compounds of the inventions and

  本发明涉及用于治疗结核病的抑制剂化合物。该发明还提供了制备该发明化合物的方法。
• US9422271B2
  申请人：——

  公开号：US9422271B2

  公开（公告）日：2016-08-23