2-Nitro-6-pyrimidin-2-yl-4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenylamine | 797047-20-2

• 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-Nitro-6-pyrimidin-2-yl-4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenylamine
• 英文别名: 2-Nitro-6-pyrimidin-2-yl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine；2-nitro-6-pyrimidin-2-yl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline
• CAS: 797047-20-2
• 化学式: C₁₆H₁₉BN₄O₄
• 分子量: 342.162
• InChiKey: MSSVCWCXGFOAOI-UHFFFAOYSA-N

物化性质

• 沸点：
  452.3±45.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.93
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-Nitro-6-pyrimidin-2-yl-4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenylamine 在 四(三苯基膦)钯 、 甲烷磺酸 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-[2-[[(Ethylamino)carbonyl]amino]-7-(2-pyrimidinyl)-1H-benzimidazol-5-yl]-2-pyridinecarboxamide
  参考文献：
  名称：

  Successful application of serum shift prediction models to the design of dual targeting inhibitors of bacterial gyrase B and topoisomerase IV with improved in vivo efficacy

  摘要：

  A series of dual targeting inhibitors of bacterial gyrase B and topoisomerase IV were identified and optimized to mid-to-low nanomolar potency against a variety of bacteria. However, in spite of seemingly adequate exposure achieved upon IV administration, the in vivo efficacy of the early lead compounds was limited by high levels of binding to serum proteins. To overcome this limitation, targeted serum shift prediction models were generated for each subclass of interest and were applied to the design of prospective analogs. As a result, numerous compounds with comparable antibacterial potency and reduced protein binding were generated. These efforts culminated in the synthesis of compound 10, a potent inhibitor with low serum shift that demonstrated greatly improved in vivo efficacy in two distinct rat infection models. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.022
• 作为产物：
  描述：

  2,2-dimethyl-N-(2-pyrimidin-2-yl-phenyl)-propionamide 在 四(三苯基膦)钯 、 溴 、 potassium acetate 、 sodium acetate 作用下， 以 1,4-二氧六环 、 溶剂黄146 为溶剂， 生成 2-Nitro-6-pyrimidin-2-yl-4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenylamine
  参考文献：
  名称：

  Successful application of serum shift prediction models to the design of dual targeting inhibitors of bacterial gyrase B and topoisomerase IV with improved in vivo efficacy

  摘要：

  A series of dual targeting inhibitors of bacterial gyrase B and topoisomerase IV were identified and optimized to mid-to-low nanomolar potency against a variety of bacteria. However, in spite of seemingly adequate exposure achieved upon IV administration, the in vivo efficacy of the early lead compounds was limited by high levels of binding to serum proteins. To overcome this limitation, targeted serum shift prediction models were generated for each subclass of interest and were applied to the design of prospective analogs. As a result, numerous compounds with comparable antibacterial potency and reduced protein binding were generated. These efforts culminated in the synthesis of compound 10, a potent inhibitor with low serum shift that demonstrated greatly improved in vivo efficacy in two distinct rat infection models. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.022

文献信息

• Gyrase inhibitors and uses thereof
  申请人：——

  公开号：US20040235886A1

  公开（公告）日：2004-11-25

  The present invention relates to compounds which inhibit bacterial gyrase and/or Topo IV and pharmaceutically acceptable compositions comprising said compounds. These compounds, and compositions thereof, are useful in treating bacterial infection. Accordingly, the present invention also relates to methods for treating bacterial infections in mammals.

  本发明涉及抑制细菌旋转酶和/或Topo IV的化合物以及包含该类化合物的药学上可接受的组合物。这些化合物及其组合物在治疗细菌感染方面具有用途。因此，本发明还涉及治疗哺乳动物细菌感染的方法。
• GYRASE INHIBITORS AND USES THEREOF
  申请人：Charifson PAUL

  公开号：US20090325955A1

  公开（公告）日：2009-12-31

  The present invention relates to methods of treating, preventing, or lessening the severity of resistant bacterial infections in mammals, utilizing compounds of formula I or formula VII or pharmaceutically salts thereof. The present invention also relates to methods of using compounds of formula I or formula VII in combination with one or more additional antibacterial agents and/or one or more additional therapeutic agents that increase the susceptibility of bacterial organisms to antibiotics.

  本发明涉及使用化合物I或化合物VII或其药学盐在哺乳动物中治疗、预防或减轻耐药细菌感染的方法。本发明还涉及使用化合物I或化合物VII与一个或多个额外的抗菌剂和/或一个或多个增加细菌对抗生素敏感性的治疗剂相结合的方法。
• Gyrase Inhibitors and Uses Thereof
  申请人：Charifson Paul

  公开号：US20120010222A1

  公开（公告）日：2012-01-12

  The present invention relates to methods of treating, preventing, or lessening the severity of resistant bacterial infections in mammals, utilizing compounds of formula I or formula VII or pharmaceutically salts thereof. The present invention also relates to methods of using compounds of formula I or formula VII in combination with one or more additional antibacterial agents and/or one or more additional therapeutic agents that increase the susceptibility of bacterial organisms to antibiotics.

  本发明涉及使用I式或VII式化合物或其药学盐治疗、预防或减轻哺乳动物中耐药细菌感染的方法。本发明还涉及使用I式或VII式化合物与一种或多种额外的抗菌剂和/或一种或多种增加细菌对抗生素易感性的治疗剂联合使用的方法。
• WO2007/56330
  申请人：——

  公开号：——

  公开（公告）日：——