6-O-methyl-9a-aza-9a-homoerythromycin A | 210912-02-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-O-methyl-9a-aza-9a-homoerythromycin A
• 英文别名: clarithromycin 9a-lactam；(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecane-7,15-dione
• CAS: 210912-02-0
• 化学式: C₃₈H₇₀N₂O₁₃
• 分子量: 762.979
• InChiKey: DKJDMFKBFWCHQJ-VIARIJRMSA-N

物化性质

• 沸点：
  847.6±65.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  53
• 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：
  195
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  clarithromycin 9(E)-oxime 在 邻甲苯磺酰氯 、 碳酸氢钠 、 potassium hydroxide 作用下， 以 丙酮 、 水 为溶剂， 反应 0.33h， 以83.5%的产率得到6-O-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Anti-Infammatory Macrolide

  摘要：

  化合物3'-N-去甲基-4"-O-(2-二乙基氨基乙酰基)-6-O-甲基-9a-氮杂-9a-同异红霉素A，具有化学式（I）或其盐，包含该化合物的组合物，其在治疗中性粒细胞主导的炎症性疾病中的用途，以及其制备方法。

  公开号：

  US20100197623A1

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.
• [EN] NEW 14 AND 15 MEMBERED MACROLIDES FOR THE TREATMENT OF NEUTROPHIL DOMINATED INFLAMMATORY DISEASES<br/>[FR] NOUVEAUX MACROLIDES À 14 ET 15 CHAÎNONS POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES À DOMINANCE EN NEUTROPHILES
  申请人：GLAXO GROUP LTD

  公开号：WO2011131749A1

  公开（公告）日：2011-10-27

  (E)-11,12-Didehydro-11,12-dideoxy 14-membered macrolides and 15-membered azalide macrolides represented by Formula (I): useful in the treatment of neutrophil dominated inflammatory diseases, especially in the 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 methods for their preparation, to their use as therapeutic agents, and to salts thereof.

  (E)-11,12-二去氢-11,12-二脱氧14-元大环内酯和15-元氮代大环内酯，由化学式(I)代表：用于治疗中性粒细胞主导的炎症性疾病，特别是用于治疗由中性粒细胞浸润引起的中性粒细胞主导的炎症性疾病和/或与中性粒细胞细胞功能改变有关的疾病，以及用于其制备的中间体，其制备方法，其用作治疗剂的用途，以及其盐。
• 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。
• Novel Tandem Reaction for the Synthesis of N′-Substituted 2-Imino-1,3-oxazolidines from Vicinal (sec- or tert-)Amino Alcohol of Desosamine
  作者：Ines Vujasinović、Zorica Marušić Ištuk、Samra Kapić、Mirjana Bukvić Krajačić、Antun Hutinec、Ivica Đilović、Dubravka Matković-Čalogović、Goran Kragol

  DOI：10.1002/ejoc.201001707

  日期：2011.5

  2-imino-1, 3-oxazolidine structures. The yields of both one-pot methods are comparable to the yield of the sequential reaction. A small library of a new class of desosamine-modified 14- and 15-membered macrolides was prepared to demonstrate the variety of substituents that can be easily introduced and thus enable a huge variation of the physicochemical and hence biological properties of these new molecules

  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。
• [EN] SECO MACROLIDE COMPOUNDS<br/>[FR] COMPOSÉS MACROLIDES DE TYPE SECO
  申请人：FIDELTA D O O

  公开号：WO2017194452A1

  公开（公告）日：2017-11-16

  The present invention relates to seco (opened ring) macrolide compounds of formula (I), to the process for preparation thereof, to the use of said seco macrolide compounds as intermediates for preparation of macrolide based macrocycles, to macrolide based macrocycles obtained from said seco macrolide compounds, to the process for preparation of macrolide based macrocycles, to the pharmaceutical compositions comprising macrolide based macrocycles, and to the use of macrolide based macrocycles as therapeutic agents.

  本发明涉及具有式(I)的开环（seco）大环内酯化合物，其制备方法，所述开环大环内酯化合物作为制备基于大环内酯的中间体的用途，从所述开环大环内酯化合物获得的基于大环内酯的大环内酯，制备基于大环内酯的大环内酯的方法，包括基于大环内酯的大环内酯的制药组合物，以及基于大环内酯的大环内酯作为治疗剂的用途。