阿兰西那 | 150785-53-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 阿兰西那
• 中文别名: 8,9-二脱氢-3'N-脱甲基-9-脱羰基-4'',6,12-三脱氧-6,9-环氧-3'N-乙基赤藓霉素
• 英文名称: ABT-229
• 英文别名: Alemcinal；(2R,3S,4R,5R,8R,9S,10S,11R,12R)-5-ethyl-11-[(2S,3R,4S,6R)-4-[ethyl(methyl)amino]-3-hydroxy-6-methyloxan-2-yl]oxy-3-hydroxy-9-[(2S,4S,6S)-4-methoxy-4,6-dimethyloxan-2-yl]oxy-2,4,8,10,12,14-hexamethyl-6,15-dioxabicyclo[10.2.1]pentadec-1(14)-en-7-one
• CAS: 150785-53-8
• 化学式: C₃₈H₆₇NO₁₀
• 分子量: 697.951
• InChiKey: IWTSXJNGTTXMFK-KTQUSEMZSA-N

物化性质

• 沸点：
  758.9±60.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  49
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  阿兰西那 在 四丙基高钌酸铵 、 4 A molecular sieve 、 N-甲基吗啉氧化物 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 4.0h， 生成 C₄₀H₆₇NO₁₁
  参考文献：
  名称：

  3H-labeling of prokinetic motilide ABT-229 for biodistribution and metabolism studies

  摘要：

  The prokinetic drug candidate, ABT-229, has been successfully [H-3]-labeled in the marolactone ring. This was accomplished with [H-3]-NaBH4 reduction of the 11-ketone analog in a four step synthetic sequence beginning with the drug candidate. The H-3-labeled drug was obtained with specific activity of 9.0 Ci/mmol and radiochemical purity >99%. This constitutes the first methodology for H-3-labeling of the macrolactone in an erythromycin derivative.

  DOI：

  10.1002/(sici)1099-1344(199607)38:7<687::aid-jlcr889>3.0.co;2-q
• 作为产物：
  描述：

  红霉素B 在 二氯乙酸 、 4-二甲氨基吡啶 、 偶氮二异丁腈 、 碘 、 三正丁基氢锡 、 sodium acetate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 52.75h， 生成 阿兰西那
  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

• J. Med. Chem. 1995, 38, 1793-1798
  作者：

  DOI：——

  日期：——
• 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.
• 3H-labeling of prokinetic motilide ABT-229 for biodistribution and metabolism studies
  作者：Ramin Faghih、Cynthia Burnell-Curty、Bruce Surber、Simin Shoghi、Anthony Borre、Ye Yao、Paul A. Lartey、Hugh N. Nellans

  DOI：10.1002/(sici)1099-1344(199607)38:7<687::aid-jlcr889>3.0.co;2-q

  日期：1996.7

  The prokinetic drug candidate, ABT-229, has been successfully [H-3]-labeled in the marolactone ring. This was accomplished with [H-3]-NaBH4 reduction of the 11-ketone analog in a four step synthetic sequence beginning with the drug candidate. The H-3-labeled drug was obtained with specific activity of 9.0 Ci/mmol and radiochemical purity >99%. This constitutes the first methodology for H-3-labeling of the macrolactone in an erythromycin derivative.