3-chloro-6-[(2R,6R)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: 3-chloro-6-[(2R,6R)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde
• 英文别名: 3-chloro-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde
• 化学式: C₁₄H₁₄ClFN₂O₃
• 分子量: 312.728
• InChiKey: CTOCASDBZCPZAF-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-chloro-6-[(2R,6R)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde 在 4-甲基苯磺酸吡啶 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 22.16h， 生成 (2R,4S,4aS)-8-[(4S)-4-(ethoxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2'H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5'-pyrimidine]-2',4',6'(1'H,3'H)-trione
  参考文献：
  名称：

  COMPOUNDS AND METHODS FOR TREATING BACTERIAL INFECTIONS

  摘要：

  化合物的结构式（I），其药学上可接受的盐，以及利用该结构式（I）化合物治疗细菌感染的用途被披露。

  公开号：

  US20140206677A1
• 作为产物：
  描述：

  6,7-difluoro-1,2-benzisoxazol-3(2H)-one 在 2,2,6,6-四甲基哌啶 、 正丁基锂 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 反应 8.75h， 生成 3-chloro-6-[(2R,6R)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde
  参考文献：
  名称：

  Novel DNA Gyrase Inhibiting Spiropyrimidinetriones with a Benzisoxazole Scaffold: SAR and in Vivo Characterization

  摘要：

  The compounds described herein with a spirocyclic architecture fused to a benzisoxazole ring represent a new class of antibacterial agents that operate by inhibition of DNA gyrase as corroborated in an enzyme assay and by the inhibition of precursor thymidine into DNA during cell growth. Activity resided in the configurationally lowest energy (2S,4R,4aR) diastereomer. Highly active compounds against Staphylococcus aureus had sufficiently high solubility, high plasma protein free fraction, and favorable pharmacokinetics to suggest that in vivo efficacy could be demonstrated, which was realized with compound (-)-1 in S. aureus mouse infection models. A high drug exposure NOEL on oral dosing in the rat suggested that a high therapeutic margin could be achieved. Importantly, (-)-1 was not cross-resistant with other DNA gyrase inhibitors such as fluoroquinolone and aminocoumarin antibacterials. Hence, this class shows considerable promise for the treatment of infections caused by multidrug resistant bacteria, including S. aureus.

  DOI：

  10.1021/jm501174m

文献信息

• [EN] FUSED, SPIROCYCLIC HETEROAROMATIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS HÉTÉROAROMATIQUES SPIROCYCLIQUES FUSIONNÉS POUR TRAITER LES INFECTIONS BACTÉRIENNES
  申请人：ASTRAZENECA AB

  公开号：WO2010043893A1

  公开（公告）日：2010-04-22

  The present invention relates to compounds of Formula (I); to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to methods for their preparation.

  本发明涉及式(I)的化合物；其药学上可接受的盐；使用它们治疗细菌感染的方法；以及它们的制备方法。
• FUSED, SPIROCYCLIC HETEROAROMATIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
  申请人：Barvian Kevin

  公开号：US20110245224A1

  公开（公告）日：2011-10-06

  The present invention relates to compounds of Formula (I); to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to methods for their preparation.

  本发明涉及式(I)的化合物；其药学上可接受的盐；使用它们治疗细菌感染的方法；以及它们的制备方法。
• Fused, spirocyclic heteroaromatic compounds for the treatment of bacterial infections
  申请人：Barvian Kevin

  公开号：US08658641B2

  公开（公告）日：2014-02-25

  The present invention relates to compounds of Formula (I); to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to methods for their preparation.

  本发明涉及以下式（I）的化合物；其药学上可接受的盐；使用它们治疗细菌感染的方法；以及它们的制备方法。
• Compounds and methods for treating bacterial infections
  申请人：AstraZeneca AB

  公开号：US08889671B2

  公开（公告）日：2014-11-18

  Compounds of formula (I), pharmaceutically acceptable salts thereof, and uses of the compounds of formula (I) for treating bacterial infections are disclosed.

  公开了式（I）的化合物，其药学上可接受的盐，以及使用式（I）的化合物治疗细菌感染的用途。
• CHEMICAL COMPOUNDS 542
  申请人：ASTRAZENECA AB

  公开号：US20140128371A1

  公开（公告）日：2014-05-08

  The present invention relates to compounds of Formula (I): to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to methods for their preparation.

  本发明涉及式（I）的化合物，其中：制备这些化合物的方法，以及将其用于治疗细菌感染的方法和其制备方法的药学上可接受的盐。