[(2R,3S,4E,7R,9R,10R,11R,13R)-10-[(2S,3R,4S,6R)-3-benzoyloxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-3-ethenyl-2-ethyl-9-methoxy-5,7,9,11,13-pentamethyl-6,12,14-trioxo-1-oxacyclotetradec-4-en-3-yl] imidazole-1-carboxylate | 484671-61-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2R,3S,4E,7R,9R,10R,11R,13R)-10-[(2S,3R,4S,6R)-3-benzoyloxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-3-ethenyl-2-ethyl-9-methoxy-5,7,9,11,13-pentamethyl-6,12,14-trioxo-1-oxacyclotetradec-4-en-3-yl] imidazole-1-carboxylate
• CAS: 484671-61-6
• 化学式: C₄₂H₅₇N₃O₁₁
• 分子量: 779.928
• InChiKey: FXSSINRFQDEDEB-YTQRJIGNSA-N

物化性质

• 沸点：
  846.0±75.0 °C(predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  56
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  162
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  [(2R,3S,4E,7R,9R,10R,11R,13R)-10-[(2S,3R,4S,6R)-3-benzoyloxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-3-ethenyl-2-ethyl-9-methoxy-5,7,9,11,13-pentamethyl-6,12,14-trioxo-1-oxacyclotetradec-4-en-3-yl] imidazole-1-carboxylate 在 甲醇 作用下， 以 水 、 乙腈 为溶剂， 反应 28.0h， 生成 (3aS,4R,7R,9R,10R,11S,13R,15R,15aR)-4-ethyl-1-[4-(3H-imidazo[4,5-b]pyridin-3-yl)butyl]-11-methoxy-7,9,11,13,15-pentamethyl-2,6,8,14-tetraoxo-3a-vinyltetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl-3,4,6-trideoxy-3-(dimethylamino)-D-xylo-hexopyranoside
  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 、 N-氯代丁二酰亚胺 、 四氧化锇 、 氯化亚砜 、 二甲基硫 、 4-甲基苯磺酸吡啶 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 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 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 172.0h， 生成 [(2R,3S,4E,7R,9R,10R,11R,13R)-10-[(2S,3R,4S,6R)-3-benzoyloxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-3-ethenyl-2-ethyl-9-methoxy-5,7,9,11,13-pentamethyl-6,12,14-trioxo-1-oxacyclotetradec-4-en-3-yl] imidazole-1-carboxylate
  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
• Synthesis and Antibacterial Activity of Novel C₁₂ Vinyl Ketolides
  作者：Matthew T. Burger、Xiaodong Lin、Daniel T. Chu、Christy Hiebert、Alice C. Rico、Mehran Seid、Georgia L. Carroll、Lynn Barker、Kay Huh、Mike Langhorne、Ribhi Shawar、Jolene Kidney、Kelly Young、Scott Anderson、Manoj C. Desai、Jacob J. Plattner

  DOI：10.1021/jm051157a

  日期：2006.3.1

  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.