[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11E,13R,14R)-14-ethyl-4,13-dihydroxy-13-(hydroxymethyl)-7-methoxy-3,5,7,9,11-pentamethyl-2,10-dioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] benzoate | 484671-58-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11E,13R,14R)-14-ethyl-4,13-dihydroxy-13-(hydroxymethyl)-7-methoxy-3,5,7,9,11-pentamethyl-2,10-dioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] benzoate
• CAS: 484671-58-1
• 化学式: C₃₇H₅₇NO₁₁
• 分子量: 691.86
• InChiKey: QLSOIDVOXBQRHK-FDKHUMLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  49
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11E,13R,14R)-14-ethyl-4,13-dihydroxy-13-(hydroxymethyl)-7-methoxy-3,5,7,9,11-pentamethyl-2,10-dioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] benzoate 在 N-氯代丁二酰亚胺 、 二甲基硫 、 双(三甲基硅烷基)氨基钾 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 生成 [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,5R,6R,7R,9R,11E,13S,14R)-13-ethenyl-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11-pentamethyl-2,4,10-trioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] benzoate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel C₁₂ Vinyl Ketolides

  摘要：

  A novel series Of C-12 vinyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens. The C-12 modification involves replacing the natural C-12 methyl group in the erythromycin core with a vinyl group via chemical synthesis. From the C-12 vinyl macrolide core, a series Of C-12 vinyl ketolides was prepared. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria. The C-12 vinyl ketolides 6j and 6k showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. However, the pharmacokinetic profiles Of C-12 vinyl ketolides 6j and 6k in rats differ from that of telithromycin by having higher lung-to-plasma ratios, larger volumes of distribution, and longer half-lives. These pharmacokinetic differences have a pharmacodynamic effect as both 6j and 6k exhibited better in vivo efficacy than telithromycin in rat lung infection models against Streptococcus pneumoniae and Haemophilus influenzae.

  DOI：

  10.1021/jm051157a
• 作为产物：
  描述：

  克拉霉素 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 2-二甲氨基嘧啶 、 sodium tetrahydroborate 、 四氧化锇 、 氯化亚砜 、 4-甲基苯磺酸吡啶 、 戴斯-马丁氧化剂 、 N-甲基吗啉氧化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 、 叔丁醇 为溶剂， 反应 159.0h， 生成 [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11E,13R,14R)-14-ethyl-4,13-dihydroxy-13-(hydroxymethyl)-7-methoxy-3,5,7,9,11-pentamethyl-2,10-dioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] benzoate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel C₁₂ Vinyl Ketolides

  摘要：

  A novel series Of C-12 vinyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens. The C-12 modification involves replacing the natural C-12 methyl group in the erythromycin core with a vinyl group via chemical synthesis. From the C-12 vinyl macrolide core, a series Of C-12 vinyl ketolides was prepared. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria. The C-12 vinyl ketolides 6j and 6k showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. However, the pharmacokinetic profiles Of C-12 vinyl ketolides 6j and 6k in rats differ from that of telithromycin by having higher lung-to-plasma ratios, larger volumes of distribution, and longer half-lives. These pharmacokinetic differences have a pharmacodynamic effect as both 6j and 6k exhibited better in vivo efficacy than telithromycin in rat lung infection models against Streptococcus pneumoniae and Haemophilus influenzae.

  DOI：

  10.1021/jm051157a

文献信息

• [EN] PYRIDYL SUBSTITUTED KETOLIDE ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES A BASE DE KETOLIDE A SUBSTITUTION PYRIDYLE
  申请人：CHIRON CORP

  公开号：WO2004096822A3

  公开（公告）日：2004-12-16