4''-deoxy-erythromycin B | 86405-13-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4''-deoxy-erythromycin B
• 英文别名: 4"-deoxyerythromycin；4"-deoxyerythromycin B；(3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12-dihydroxy-4-[(2S,4S,6S)-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• CAS: 86405-13-2
• 化学式: C₃₇H₆₇NO₁₁
• 分子量: 701.939
• InChiKey: SDKIILJFLGANRR-POQOJAKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4''-deoxy-erythromycin B 在 碘 、 sodium acetate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以81%的产率得到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
• 作为产物：
  描述：

  红霉素B 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 38.75h， 生成 4''-deoxy-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

文献信息

• PROCESS FOR N-DESMETHYLATING ERYTHROMYCINS AND DERIVATIVES THEREOF
  申请人：Abbott Laboratories

  公开号：EP1032580B1

  公开（公告）日：2004-03-31
• Efficient Large-Scale Radical Deoxygenation in Alcoholic Solvents Using Sodium Hypophosphite and a Phase-Transfer Agent:  Application to Erythromycins
  作者：Alexandra E. Graham、Albert V. Thomas、Rachel Yang

  DOI：10.1021/jo991645o

  日期：2000.4.1
• Facile N-demethylation of erythromycins
  作者：John E. Hengeveld、Ashok K. Gupta、Anne H. Kemp、Albert V. Thomas

  DOI：10.1016/s0040-4039(99)00244-0

  日期：1999.3

  4 "-Deoxyerythromycin B reacts with 1-chloroethyl chloroformate to give the corresponding N-demethyl N-chloroethyl carbamate, Mild methanolysis removes the chloroethyl group giving the N-demethyl erythromycin derivative while also forming the 6,9-enol ether moiety. Further manipulation gives ABT-229, a potential prokinetic agent. (C) 1999 Elsevier Science Ltd. All rights reserved.
• 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.