tert-butyl ((3S,6R)-6-(((1-phenyl-1H-tetrazol-5-yl)sulfonyl)-methyl)tetrahydro-2H-pyran-3-yl)carbamate | 881657-99-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl ((3S,6R)-6-(((1-phenyl-1H-tetrazol-5-yl)sulfonyl)-methyl)tetrahydro-2H-pyran-3-yl)carbamate
• 英文别名: tert-butyl N-[(3S,6R)-6-[(1-phenyltetrazol-5-yl)sulfonylmethyl]oxan-3-yl]carbamate
• CAS: 881657-99-4
• 化学式: C₁₈H₂₅N₅O₅S
• 分子量: 423.493
• InChiKey: GRCYJTGPLQQLOX-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl ((3S,6R)-6-(((1-phenyl-1H-tetrazol-5-yl)sulfonyl)-methyl)tetrahydro-2H-pyran-3-yl)carbamate 在 甲基磺酰胺 、 双(三甲基硅烷基)氨基钾 作用下， 以 乙二醇二甲醚 、 水 、 乙酸乙酯 、 甲苯 、 叔丁醇 为溶剂， 反应 0.5h， 生成 tert-butyl N-[(3S,6R)-6-[(1R,2S)-1,2-dihydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]oxan-3-yl]carbamate
  参考文献：
  名称：

  Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity

  摘要：

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.

  DOI：

  10.1021/jm400963y
• 作为产物：
  描述：

  (S)-2-tert-butoxycarbonylamino-hex-5-enoic acid methyl ester 在 4-二甲氨基吡啶 、 锂硼氢 、 hexaammonium heptamolybdate tetrahydrate 、 camphor-10-sulfonic acid 、 双氧水 、 三乙胺 、 间氯过氧苯甲酸 、 sodium iodide 、 potassium hydroxide 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 39.0h， 生成 tert-butyl ((3S,6R)-6-(((1-phenyl-1H-tetrazol-5-yl)sulfonyl)-methyl)tetrahydro-2H-pyran-3-yl)carbamate
  参考文献：
  名称：

  Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity

  摘要：

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.

  DOI：

  10.1021/jm400963y

文献信息

• NEW BICYCLIC ANTIBIOTICS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1799676A2

  公开（公告）日：2007-06-27
• [EN] NEW BICYCLIC ANTIBIOTICS<br/>[FR] NOUVEAUX ANTIBIOTIQUES BICYCLIQUES
  申请人：ACTELION PERCUREX AG

  公开号：WO2006032466A2

  公开（公告）日：2006-03-30

  The invention relates to novel antibiotics of formula (I) wherein R1 represents alkyl, alkoxy, haloalkoxy, halogen or cyano; one or two of U, V, W and X represent(s) N, the remaining represent CH, or, in case of U, V and/or W, may also represent CRa and, in the case of X, may also represent CRb; Ra represents halogen; Rb represents halogen or alkoxy; M is a linking chain containing a non-aromatic cyclic or heterocyclic group, and D represents alkyl, aryl or heteroaryl.
• Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity
  作者：Jean-Philippe Surivet、Cornelia Zumbrunn、Georg Rueedi、Christian Hubschwerlen、Daniel Bur、Thierry Bruyère、Hans Locher、Daniel Ritz、Wolfgang Keck、Peter Seiler、Christopher Kohl、Jean-Christophe Gauvin、Azely Mirre、Verena Kaegi、Marina Dos Santos、Mika Gaertner、Jonathan Delers、Michel Enderlin-Paput、Maria Boehme

  DOI：10.1021/jm400963y

  日期：2013.9.26

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.