2'-O-acetyl-4"-(imidazolylthiocarbonyl)erythromycin B | 150785-59-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-O-acetyl-4"-(imidazolylthiocarbonyl)erythromycin B
• 英文别名: [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-14-ethyl-7,12-dihydroxy-4-[(2R,4R,5S,6S)-5-(imidazole-1-carbothioyloxy)-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-6-methyloxan-3-yl] acetate
• CAS: 150785-59-4
• 化学式: C₄₃H₇₁N₃O₁₃S
• 分子量: 870.115
• InChiKey: VSUGXKWSWOITDB-XBUMAHDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  60
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  219
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2'-O-acetyl-4"-(imidazolylthiocarbonyl)erythromycin B 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 以78%的产率得到2'-O-acetyl-4"-deoxyerythromycin B
  参考文献：
  名称：

  Synthesis of 4''-Deoxy Motilides: Identification of a Potent and Orally Active Prokinetic Drug Candidate

  摘要：

  As an approach to discovering highly potent motilides with oral activity, novel 4''-deoxy derivatives of 8,9-anhydroerythromycin 6,9-hemiacetal were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds were orders of magnitude more potent than their 4''-hydroxy analogs in inducing smooth muscle contractions in an in vitro rabbit duodenal assay. Removal of the 12-hydroxy group, which was aimed at improving oral bioavailability, also afforded further potentiation in in vitro activity, leading to the identification of 8,9-anhydro-4''-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B 6,9-hemiacetal (ABT-229) as a potential prokinetic drug. ABT-229 was >300 000 times more potent than erythromycin in, vitro and had 39% oral bioavailability in dog compared to its 4'';12-dihydroxy congener (EM-523), which was only 400 times more potent than erythromycin and had relatively low (1.4%) oral bioavailability.

  DOI：

  10.1021/jm00010a024
• 作为产物：
  描述：

  红霉素B 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 2'-O-acetyl-4"-(imidazolylthiocarbonyl)erythromycin B
  参考文献：
  名称：

  Synthesis of 4''-Deoxy Motilides: Identification of a Potent and Orally Active Prokinetic Drug Candidate

  摘要：

  As an approach to discovering highly potent motilides with oral activity, novel 4''-deoxy derivatives of 8,9-anhydroerythromycin 6,9-hemiacetal were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds were orders of magnitude more potent than their 4''-hydroxy analogs in inducing smooth muscle contractions in an in vitro rabbit duodenal assay. Removal of the 12-hydroxy group, which was aimed at improving oral bioavailability, also afforded further potentiation in in vitro activity, leading to the identification of 8,9-anhydro-4''-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B 6,9-hemiacetal (ABT-229) as a potential prokinetic drug. ABT-229 was >300 000 times more potent than erythromycin in, vitro and had 39% oral bioavailability in dog compared to its 4'';12-dihydroxy congener (EM-523), which was only 400 times more potent than erythromycin and had relatively low (1.4%) oral bioavailability.

  DOI：

  10.1021/jm00010a024