(4S,4aS,5aR,12aS)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-8-(di-2-propen-1-ylamino)-10-fluoro-11a,12,12a,13-tetrahydro-5-hydroxy-3,7-bis(phenylmethoxy)-naphthaceno[2,3-d]isoxazole-4,6(4aH,11H)-dione | 1207284-91-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (4S,4aS,5aR,12aS)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-8-(di-2-propen-1-ylamino)-10-fluoro-11a,12,12a,13-tetrahydro-5-hydroxy-3,7-bis(phenylmethoxy)-naphthaceno[2,3-d]isoxazole-4,6(4aH,11H)-dione
• CAS: 1207284-91-0
• 化学式: C₄₇H₅₄FN₃O₇Si
• 分子量: 820.046
• InChiKey: MECRVNZYZOJKPZ-SHQBIKDJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  59.0
• 可旋转键数：
  14.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  114.57
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (4S,4aS,5aR,12aS)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-8-(di-2-propen-1-ylamino)-10-fluoro-11a,12,12a,13-tetrahydro-5-hydroxy-3,7-bis(phenylmethoxy)-naphthaceno[2,3-d]isoxazole-4,6(4aH,11H)-dione 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 溶剂黄146 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 (4aS,11aR,12aS,13S)-3,7-bis(benzyloxy)-4a-((tert-butyldimethylsilyl)oxy)-13-(dimethylamino)-10-fluoro-5-hydroxy-8-(isopentylamino)-11a,12,12a,13-tetrahydrotetraceno[2,3-d]isoxazole-4,6(4aH,11H)-dione
  参考文献：
  名称：

  Fluorocyclines. 2. Optimization of the C-9 Side-Chain for Antibacterial Activity and Oral Efficacy

  摘要：

  Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain of the fluorocyclines was optimized for both antibacterial activity and oral efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A)) and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are active against Gram-positive and Gram-negative organisms. A murine systemic infection model was used as an oral efficacy screen to rapidly identify compounds with oral bioavailability. Two compounds were identified that exhibit both oral bioavailability in rat and clinically relevant bacterial susceptibility profiles against major respiratory pathogens. One compound demonstrated oral efficacy in rodent lung infection models that was comparable to marketed antibacterial agents,

  DOI：

  10.1021/jm201467r
• 作为产物：
  描述：

  (4aS,8aS,9S)-9-(二甲基氨基)-4a-[[叔丁基二甲基硅烷基]氧基]-8a,9-二氢-3-(苯基甲氧基)-萘并[2,3-d]异恶唑-4,5(4aH,8H)-二酮 、 phenyl 2-(benzyloxy)-3-[bis(prop-2-en-1-yl)amino]-5-fluoro-6-methylbenzoate 在 四甲基乙二胺 、 lithium diisopropyl amide 、 lithium hexamethyldisilazane 、 水 、 氯化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以41%的产率得到(4S,4aS,5aR,12aS)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-8-(di-2-propen-1-ylamino)-10-fluoro-11a,12,12a,13-tetrahydro-5-hydroxy-3,7-bis(phenylmethoxy)-naphthaceno[2,3-d]isoxazole-4,6(4aH,11H)-dione
  参考文献：
  名称：

  [EN] C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS
  [FR] COMPOSÉS DE TÉTRACYCLINE C7-FLUOROSUBSTITUÉE

  摘要：

  本发明涉及一种由结构式（A）表示的化合物，或其药学上可接受的盐。结构式（A）的变量在此处定义。还描述了包括结构式（A）化合物的药物组合物及其治疗用途。

  公开号：

  WO2010017470A1