[(2R,5S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]oxan-2-yl]methyl 4-methylbenzenesulfonate | 881657-57-4

• 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: [(2R,5S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]oxan-2-yl]methyl 4-methylbenzenesulfonate
• CAS: 881657-57-4
• 化学式: C₁₈H₂₇NO₆S
• 分子量: 385.481
• InChiKey: YMPAYOISXVBDBR-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(2R,5S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]oxan-2-yl]methyl 4-methylbenzenesulfonate 在 hexaammonium heptamolybdate tetrahydrate 、 双氧水 、 sodium iodide 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 28.0h， 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
• 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 、 camphor-10-sulfonic acid 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 11.0h， 生成 [(2R,5S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]oxan-2-yl]methyl 4-methylbenzenesulfonate
  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

• 3-AMINO-6-(1-AMINO-ETHYL)-TETRAHYDROPYRAN DERIVATIVES
  申请人：Hubschwerlen Christian

  公开号：US20100179135A1

  公开（公告）日：2010-07-15

  Antibacterial compounds including 3-amino-6-(1-amino-ethyl)-tetrahydropyran derivatives are provided, and methods of treatment or prevention of bacterial infection with such compounds are provided.

  提供了包括3-氨基-6-(1-氨乙基)-四氢吡喃衍生物在内的抗菌化合物，并提供了使用这些化合物进行治疗或预防细菌感染的方法。
• US8193179B2
  申请人：——

  公开号：US8193179B2

  公开（公告）日：2012-06-05
• [EN] 3-AMINO-6-(1-AMINO-ETHYL)-TETRAHYDROPYRAN DERIVATIVES<br/>[FR] DÉRIVÉS DE 3-AMINO-6-(1-AMINO-ÉTHYL)-TÉTRAHYDROPYRANE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2008152603A1

  公开（公告）日：2008-12-18

  [EN] The invention relates to antibacterial compounds of formula I wherein R1 represents halogen or alkoxy; U and W each represent N, V represents CH and R2 represents H or F, or U and V each represent CH, W represents N and R2 represents H or F, or U represents N, V represents CH, W represents CH or CRa and R2 represents H, or also, when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents the group CH=CH-B, a binuclear heterocyclic system D, a phenyl group which is mono substituted in position 4 by alkyl, or a phenyl group which is disubstituted in positions 3 and 4, wherein each of the substituents is independently selected from alkyl and halogen, B representing a mono- or di-substituted phenyl group wherein each substituent is a halogen atom and D representing the group wherein Z represents CH or N, and Q represents O or S; and to salts of such compounds.
  [FR] L'invention porte sur des composés antibactériens représentés par la formule (I) dans laquelle R1 représente halogène ou alcoxy; U et W représentent chacun N, V représente CH et R2 représente H ou F, ou U et V représentent chacun CH, W représente N et R2 représente H ou F, ou U représente N, V représente CH, W représente CH ou CRa et R2 représente H, ou également, lorsque W représente CH, peut représenter F; Ra représente CH2OH ou alcoxycarbonyle; A représente le groupe CH=CH-B, un système hétérocyclique binucléaire D, un groupe phényle qui est monosubstitué en position 4 par alkyle, ou un groupe phényle disubstitué dans les positions 3 et 4, chacun des substituants étant choisi indépendamment parmi alkyle et halogène, B représentant un groupe phényle mono- ou disubstitué, chaque substituant étant un atome d'halogène et D représentant le groupe dans lequel Z représente CH ou N, et Q représente O ou S. L'invention porte également sur les sels de tels composés.
• 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.