4"-deoxy-3'-N-desmethylerythromycin B | 163131-10-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4"-deoxy-3'-N-desmethylerythromycin B
• 英文别名: (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-14-ethyl-7,12-dihydroxy-6-[(2S,3R,4S,6R)-3-hydroxy-6-methyl-4-(methylamino)oxan-2-yl]oxy-4-[(2S,4S,6S)-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• CAS: 163131-10-0
• 化学式: C₃₆H₆₅NO₁₁
• 分子量: 687.912
• InChiKey: WCDDKRKFISUVEU-SUQJLRRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  48
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4"-deoxy-3'-N-desmethylerythromycin B 在 二氯乙酸 作用下， 以 乙腈 为溶剂， 反应 7.0h， 以94%的产率得到8,9-anhydro-4"-deoxy-3-N-desmethylerythromycin B 6,9-hemiacetal
  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 、 偶氮二异丁腈 、 碘 、 三正丁基氢锡 、 sodium acetate 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 45.75h， 生成 4"-deoxy-3'-N-desmethylerythromycin 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

文献信息

• Synthesis of 4''-Deoxy Motilides: Identification of a Potent and Orally Active Prokinetic Drug Candidate
  作者：Paul A. Lartey、Hugh N. Nellans、Ramin Faghih、Albert Petersen、Carla M. Edwards、Leslie Freiberg、Sherry Quigley、Kennan Marsh、Larry L Klein、Plattner Jacob J.

  DOI：10.1021/jm00010a024

  日期：1995.5

  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.