3'-N-demethyl-6-O-methyl-9a-aza-9a-homoerythromycin A | 906452-70-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3'-N-demethyl-6-O-methyl-9a-aza-9a-homoerythromycin A
• 英文别名: (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-11-[(2S,3R,4S,6R)-3-hydroxy-6-methyl-4-(methylamino)oxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecane-7,15-dione
• CAS: 906452-70-8
• 化学式: C₃₇H₆₈N₂O₁₃
• 分子量: 748.953
• InChiKey: VWUWTRFKMAABSQ-XBWOTNPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  52
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  204
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  3'-N-demethyl-6-O-methyl-9a-aza-9a-homoerythromycin A 在 碘 、 sodium methylate 、 三羟甲基氨基甲烷 作用下， 以 甲醇 为溶剂， 以45%的产率得到3'-N,N-didemethyl-6-O-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Novel desosamine-modified 14- and 15-membered macrolides without antibacterial activity

  摘要：

  Novel modifications of the desosamine sugar of 14- and 15-membered antibacterial macrolides, in which the desosamine was fused with N-substituted-1,3-oxazolidin-2-ones, were developed in order to completely suppress antibacterial activity and make them promising agents for other biological targets. The synthesis of such bicyclic desosamine derivatives, especially 1,3-oxazolidin-2-one formation, was optimized and conducted under mild conditions without a need for protection/deprotection steps for other functional groups. A focused series of novel desosamine-modified macrolide derivatives was prepared and their antibacterial activities tested. It was shown that these macrolide derivatives do not possess any residual antibacterial activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.076
• 作为产物：
  描述：

  6-O-methyl-9a-aza-9a-homoerythromycin A 在 碘 、 sodium acetate 作用下， 以 甲醇 为溶剂， 以7.3 g的产率得到3'-N-demethyl-6-O-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  从 Desosamine 的邻位（仲或叔）氨基醇合成 N'-取代的 2-Imino-1,3-恶唑烷的新型串联反应

  摘要：

  两种一锅法，顺序和串联，用于从脱糖胺的连位（仲或叔）-氨基醇通过中间烷基-、芳基-、杂芳基制备 N'-取代的 2-亚氨基-1, 3-恶唑烷-，和杂烷基硫脲部分被描述。特别有趣的是连位叔氨基醇的新型一锅串联反应，包括脱烷基化、硫脲形成和最终环化以产生 2-亚氨基-1, 3-恶唑烷结构。两种一锅法的产率与顺序反应的产率相当。制备了一类新的脱糖胺修饰的 14 元和 15 元大环内酯类的小型文库，以证明可以轻松引入的各种取代基，从而使这些新分子的物理化学和生物学特性发生巨大变化。

  DOI：

  10.1002/ejoc.201001707

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.
• Macrolides With Anti-Inflammatory Activity
  申请人：Culic Ognjen

  公开号：US20080221046A1

  公开（公告）日：2008-09-11

  The present invention relates to novel semi-synthetic macrolides having anti-inflammatory activity. More particularly, the invention relates to 14- and 15-membered macrolides substituted at the 4″ position, to their pharmaceutically acceptable derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions containing them and to their activity and use in the treatment of inflammatory diseases and conditions in humans and animals, especially those diseases associated with excessive secretion of TNF-α, IL-1, IL-8, IL-2 or IL-5; and/or inhibitor of excessive lymphocyte proliferation; and/or excessive granulocyte degranulation.

  本发明涉及具有抗炎活性的新型半合成大环内酯类化合物。更具体地说，该发明涉及在4″位置取代的14-和15-环大环内酯类化合物，及其药学上可接受的衍生物，用于其制备的工艺和中间体，含有它们的制剂，以及它们在治疗人类和动物的炎症性疾病和症状中的活性和用途，特别是那些与过度分泌TNF-α、IL-1、IL-8、IL-2或IL-5有关的疾病；和/或抑制过度淋巴细胞增殖；和/或过度粒细胞脱颗粒的抑制剂。
• Regioselective 2-Imino-1,3-thiazolidine vs. 2-Imino-1,3-oxazolidine Formation from the Vicinal<i>sec</i>-Amino Alcohol of Desosamine
  作者：Zorica Marušić Ištuk、Ines Vujasinovi、Ana Čikoš、Goran Kragol

  DOI：10.1002/ejoc.201300266

  日期：2013.7

  In order to optimize Mukaiyama reagent-induced cyclization of vicinal sec-amino alcohols of desosamine origin towards exclusive formation of N′-substituted-2-imino-1,3-thiazolidines via a thiocarbamoyl intermediate, the influence of reaction conditions was studied. A novel, mild, one-pot, two-step method was developed, and the formation of N′-substituted-2-imino-1,3-oxazolidines as side products was

  为了优化 Mukaiyama 试剂诱导的去糖胺来源的邻位仲氨基醇的环化，通过硫代氨基甲酰基中间体专门形成 N'-取代的-2-亚氨基-1,3-噻唑烷，研究了反应条件的影响。开发了一种新的、温和的、一锅两步的方法，并最大限度地减少了 N'-取代的-2-亚氨基-1,3-恶唑烷副产物的形成。使用基于 NMR 的构象分析明确建立了 C-2' 构型的反转。提出了反应机理。制备了一系列新型脱糖胺修饰的 14 和 15 元大环内酯类化合物，其带有与脱糖胺糖融合的 N'-烷基-2-亚氨基-1,3-噻唑烷。
• <i>N</i>′-Substituted-2′-<i>O</i>,3′-<i>N</i>-carbonimidoyl Bridged Macrolides: Novel Anti-inflammatory Macrolides without Antimicrobial Activity
  作者：Martina Bosnar、Goran Kragol、Sanja Koštrun、Ines Vujasinović、Berislav Bošnjak、Vlatka Bencetić Mihaljević、Zorica Marušić Ištuk、Samra Kapić、Boška Hrvačić、Karmen Brajša、Branka Tavčar、Dubravko Jelić、Ines Glojnarić、Donatella Verbanac、Ognjen Čulić、Jasna Padovan、Sulejman Alihodžić、Vesna Eraković Haber、Radan Spaventi

  DOI：10.1021/jm300356u

  日期：2012.7.12

  Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti-inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O,3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti-inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti-inflammatory therapeutics.
• Macrolides with Anti-Inflammatory Activity
  申请人：Alihodzic Sulejman

  公开号：US20120058963A1

  公开（公告）日：2012-03-08

  The present invention relates to novel semi-synthetic macrolides having anti-inflammatory activity. More particularly, the invention relates to 14- and 15-membered macrolides substituted at the 4″ position, to their pharmaceutically acceptable derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions containing them and to their activity and use in the treatment of inflammatory diseases and conditions in humans and animals, especially those diseases associated with excessive secretion of TNF-α, IL-1, IL-8, IL-2 or IL-5; and/or inhibitor of excessive lymphocyte proliferation; and/or excessive granulocyte degranulation.