(4S,4aS,5aR,12aS)-4-(dimethylamino)-7-fluoro-9-[(methylcarbamoyl)amino]-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide hydrochloride | 1354717-98-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: (4S,4aS,5aR,12aS)-4-(dimethylamino)-7-fluoro-9-[(methylcarbamoyl)amino]-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide hydrochloride
• CAS: 1354717-98-8
• 化学式: C₂₃H₂₅FN₄O₈*ClH
• 分子量: 540.933
• InChiKey: PUBDSXWJEQDUBK-LFFBRIKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.43
• 重原子数：
  37.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  202.52
• 氢给体数：
  7.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  (4S,4aS,5aR,12aS)-9-amino-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide 、 异氰酸甲酯 在 三乙胺 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 以32%的产率得到(4S,4aS,5aR,12aS)-4-(dimethylamino)-7-fluoro-9-[(methylcarbamoyl)amino]-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide hydrochloride
  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