3-descladinosyl-11,12-dideoxy-6-O-methyl-3-oxo-12,11-(oxycarbonyl-(1-((3-hydroxy-[1,5]naphthyridin-4-yl)-methyl)-azetidin-3-yl)-imino)-erythromycin A | 1056876-93-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-descladinosyl-11,12-dideoxy-6-O-methyl-3-oxo-12,11-(oxycarbonyl-(1-((3-hydroxy-[1,5]naphthyridin-4-yl)-methyl)-azetidin-3-yl)-imino)-erythromycin A
• 英文别名: (1S,2R,5R,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-15-[1-[(3-hydroxy-1,5-naphthyridin-4-yl)methyl]azetidin-3-yl]-9-methoxy-1,5,7,9,11,13-hexamethyl-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone
• CAS: 1056876-93-7
• 化学式: C₄₃H₆₃N₅O₁₁
• 分子量: 826.0
• InChiKey: PHBRSMBCWZLOFO-PBSXUYDUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  59
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  190
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  3-descladinosyl-11,12-dideoxy-6-O-methyl-3-oxo-12,11-(oxycarbonyl-(1-((3-hydroxy-[1,5]naphthyridin-4-yl)-methyl)-azetidin-3-yl)-imino)-erythromycin A 、 对甲苯磺酸 以 丙酮 为溶剂， 反应 2.0h， 以23.2 g的产率得到3-descladinosyl-11,12-dideoxy-6-O-methyl-3-oxo-12,11-(oxycarbonyl-(1-((3-hydroxy-[1,5]naphthyridin-4-yl)-methyl)-azetidin-3-yl)-imino)-erythromycin A tosylate
  参考文献：
  名称：

  Discovery of Azetidinyl Ketolides for the Treatment of Susceptible and Multidrug Resistant Community-Acquired Respiratory Tract Infections

  摘要：

  Respiratory tract bacterial strains are becoming increasingly resistant to currently marketed macrolide antibiotics. The current alternative telithromycin (1) from the newer ketolide class of macrolides addresses resistance but is hampered by serious safety concerns, hepatotoxicity in particular. We have discovered a novel series of azetidinyl ketolides that focus on mitigation of hepatotoxicity by minimizing hepatic turnover and time-dependent inactivation of CYP3A isoforms in the liver without compromising the potency and efficacy of 1.

  DOI：

  10.1021/jm900729s
• 作为产物：
  描述：

  (3-methoxy[1,5]naphthyridin-4-yl)methyl bromide 在 potassium acetate 、 三乙酰氧基硼氢化钠 、 三乙胺 、 lithium chloride 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.5h， 生成 3-descladinosyl-11,12-dideoxy-6-O-methyl-3-oxo-12,11-(oxycarbonyl-(1-((3-hydroxy-[1,5]naphthyridin-4-yl)-methyl)-azetidin-3-yl)-imino)-erythromycin A
  参考文献：
  名称：

  Process Development of a Novel Azetidinyl Ketolide Antibiotic

  摘要：

  Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.

  DOI：

  10.1021/op300064b

文献信息

• MACROLIDES
  申请人：Magee Thomas V.

  公开号：US20080293646A1

  公开（公告）日：2008-11-27

  The invention relates to compounds of Formula (I): wherein R 1 , R 2 and X are as defined herein. The invention also relates to pharmaceutical compositions and methods of treating bacterial infections using compounds of Formula (I).

  这项发明涉及到式（I）的化合物：其中R1、R2和X的定义如本文所述。该发明还涉及使用式（I）的化合物治疗细菌感染的药物组合物和方法。
• [EN] MACROLIDES<br/>[FR] MACROLIDES
  申请人：PFIZER PROD INC

  公开号：WO2008110918A2

  公开（公告）日：2008-09-18

  [EN] The invention relates to compounds of Formula (I) wherein R¹, R², and X are as defined herein. The invention also relates to pharmaceutical compositions and methods of treating bacterial infections using compounds of Formula (I).
  [FR] La présente invention concerne des composés de formule (I), R¹, R², et X étant tels que définis ici. La présente invention concerne également des compositions pharmaceutiques et des procédés de traitement d'infections bactériennes au moyen des composés de formule (I).