9-dihydro-N-desmethylerythromycin A | 654076-77-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9-dihydro-N-desmethylerythromycin A
• 英文别名: N-desmethyl-(9S)-dihydroerythromycin A；3'-N-demethyl-(9S)-9-dihydroerythromycin A；(3R,4S,5S,6R,7R,9R,10S,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-6-[(2S,3R,4S,6R)-3-hydroxy-6-methyl-4-(methylamino)oxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one
• CAS: 654076-77-4
• 化学式: C₃₆H₆₇NO₁₃
• 分子量: 721.927
• InChiKey: FMDLOBGWBPOJGJ-JWDJEKDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  50
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  206
• 氢给体数：
  7
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  9-dihydro-N-desmethylerythromycin A 在 盐酸 作用下， 以 水 为溶剂， 反应 120.0h， 以90%的产率得到
  参考文献：
  名称：

  [EN] MACROLIDE COMPOUNDS ENDOWED WITH ANTIINFLAMMATORY ACTIVITY
  [FR] COMPOSES DE MACROLIDES AYANT UNE ACTIVITE ANTI-INFLAMMATOIRE

  摘要：

  公开号：

  WO2004013153A3
• 作为产物：
  描述：

  红霉素 在 sodium tetrahydroborate 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 9-dihydro-N-desmethylerythromycin A
  参考文献：
  名称：

  Design, synthesis and in vivo activity of 9-(S)-dihydroerythromycin derivatives as potent anti-inflammatory agents

  摘要：

  The synthesis of a new class of 9-(S)-dihydroerythromycin derivatives and their anti-inflammatory activity on in vivo PMA assay are described. Modifying the desosamine sugar on the C-3' amino group, it was possible to differentiate between anti-biotic and anti-flammatory action. The compounds are completely devoid of anti-microbial effects but their anti-inflammatory properties are enhanced. These results strongly suggest the potential of macrolides as a new class of anti-inflammatory agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.076

文献信息

• [EN] 2'-O,3'-N-BRIDGED MACROLIDES<br/>[FR] MACROLIDES 2'-O,3'-N-PONTÉS
  申请人：GLAXOSMITHKLINE ZAGREB

  公开号：WO2009130189A1

  公开（公告）日：2009-10-29

  Novel 2 ' -O, 3 ' -/V-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2 ' -O, 3 ' -/V-bridged 14- membered macrolides and to 2 ' - O, 3 ' -/V-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.

  ' -O, 3 ' -/V-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2 ' -O, 3 ' -/V-bridged 14- membered macrolides and to 2 ' - O, 3 ' -/V-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.
• Motilide compounds
  申请人：Liu Yaoquan

  公开号：US20060270616A1

  公开（公告）日：2006-11-30

  Compounds having a structure according to formula (I) where R A , R B , R C , R D , R E , and R F are as defined herein, are useful as prokinetic agents.

  具有如公式（I）所示结构的化合物，其中RA、RB、RC、RD、RE和RF的定义如本文所述，可用作促动力剂。
• Motilide polymorphs
  申请人：Licari Peter J.

  公开号：US20080146654A1

  公开（公告）日：2008-06-19

  The invention provides polymorphs of a motilide having a structure represented by formula Ia

  这项发明提供了具有由化学式Ia表示的结构的莫替利德的多型体。
• 9-Dihydroerythromycins as non-antibiotic motilin receptor agonists
  作者：Yaoquan Liu、Yong Li、Yue Chen、Hao Zheng、Mark Claypool、David C. Myles、Christopher W. Carreras

  DOI：10.1016/j.bmcl.2010.08.030

  日期：2010.10

  A series of 9-dihydroerythromycin A and B analogues with modification of the desosamine nitrogen have been synthesized and screened for motilin agonist activity, antibiotic activity, tachyphylaxis and hERG channel current inhibition. Small alkyl groups resulted in the potency while compounds with a primary or secondary amine resulted in the low motilin agonist potency. Several compounds were identified as non-antibiotic motilin receptor agonists with minimal tachyphylaxis and low hERG interaction. (C) 2010 Elsevier Ltd. All rights reserved.
• Structure−Activity Relationships of 9-Substituted-9-Dihydroerythromycin-Based Motilin Agonists: Optimizing for Potency and Safety
  作者：Simon J. Shaw、Yue Chen、Hao Zheng、Hong Fu、Mark A. Burlingame、Saul Marquez、Yong Li、Mark Claypool、Christopher W. Carreras、William Crumb、Dwight J. Hardy、David C. Myles、Yaoquan Liu

  DOI：10.1021/jm901107f

  日期：2009.11.12

  A series of 9-dihydro-9-acetamido-N-desmethyl-N-isopropyl erythromycin A analogues and related derivatives was generated as motilin agonists. The compounds were optimized for potency while showing both minimal antibacterial activity and hERG inhibition. As the substituent on the amide was increased in lipophilicity the potency and hERG inhibition increased, while polar groups lowered potency, without significantly impacting hERG inhibition. The N-methyl acetamide 7a showed the optimal in vitro profile and was probed further by varying the chain length to the macrocycle as well as changing the macrocycle scaffold. 7a remained the compound with the best in vitro properties.