3'-N-(demethyl)-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A | 620169-52-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3'-N-(demethyl)-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
• 英文别名: 3'-N-Desmethyldescladinose；(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10,13-tetrahydroxy-11-[(2S,3R,4S,6R)-3-hydroxy-6-methyl-4-(methylamino)oxan-2-yl]oxy-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one
• CAS: 620169-52-0
• 化学式: C₂₉H₅₆N₂O₉
• 分子量: 576.772
• InChiKey: SZROGRUAGWWKKR-NHUOXGILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  40
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  161
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3'-N-(demethyl)-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A 在 platinum(IV) oxide 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 20.0~80.0 ℃ 、500.01 kPa 条件下， 反应 48.0h， 生成 3'-N-(demethyl)-3'-N-[3-({4-[(7-chloro-4-quinolinyl)amino]butanoyl}amino)propyl]-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Novel hybrid molecules based on 15-membered azalide as potential antimalarial agents

  摘要：

  Malaria remains the most prevalent tropical disease, and due to the spread of resistant parasites novel therapeutics are urgently needed. Azithromycin has shown potential in malaria treatment so we designed hybrid azalide molecules with the aim to improve activity against and selectivity for the malaria parasite. Novel hybrid molecules comprising 4-aminoquinoline moiety covalently liked to 15-membered azalide scaffold at position C-3' were synthesized and biologically evaluated. Antimalarial testing against Plasmodium falciparum sensitive and resistant strains confirmed the improved in vitro activity over azithromycin and chloroquine. Selectivity of the compounds (HepG2 IC50/P. falciparum IC50 ratio) for the parasite was high (100-2700) and their antibacterial activity diminished. Even though oral bioavailability determined for compound 12 was low, novel quinoline C-3'-substituted 15-membered azalides represent an interesting subclass of antimalarial macrolides that need further research and evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.039
• 作为产物：
  描述：

  阿奇霉素 在 盐酸 、 碘 、 sodium acetate 作用下， 以 甲醇 、 水 为溶剂， 反应 79.0h， 生成 3'-N-(demethyl)-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Novel hybrid molecules based on 15-membered azalide as potential antimalarial agents

  摘要：

  Malaria remains the most prevalent tropical disease, and due to the spread of resistant parasites novel therapeutics are urgently needed. Azithromycin has shown potential in malaria treatment so we designed hybrid azalide molecules with the aim to improve activity against and selectivity for the malaria parasite. Novel hybrid molecules comprising 4-aminoquinoline moiety covalently liked to 15-membered azalide scaffold at position C-3' were synthesized and biologically evaluated. Antimalarial testing against Plasmodium falciparum sensitive and resistant strains confirmed the improved in vitro activity over azithromycin and chloroquine. Selectivity of the compounds (HepG2 IC50/P. falciparum IC50 ratio) for the parasite was high (100-2700) and their antibacterial activity diminished. Even though oral bioavailability determined for compound 12 was low, novel quinoline C-3'-substituted 15-membered azalides represent an interesting subclass of antimalarial macrolides that need further research and evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.039

文献信息

• [EN] 3'-N-SUBSTITUTED 9-DEOXO-9A-METHYL-9A-AZA-HOMOERYTHROMYCIN HAVING ANTIMALARIAL ACTIVITY<br/>[FR] 9-DÉOXO-9A-MÉTHYL-9A-AZAHOMOÉRYTHROMYCINE 3'-N-SUBSTITUÉE AYANT UNE ACTIVITÉ ANTIPALUDIQUE
  申请人：GLAXOSMITHKLINE ZAGREB

  公开号：WO2010086351A1

  公开（公告）日：2010-08-05

  The present invention relates to novel 3'-N-substituted 9-deoxo-9a-methyl-9a-aza-9a- homoerythromycin A derivatives having antimalarial activity. More particularly, the invention relates to 3'-N-substituted-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A and 3'-N-substituted-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A derivatives having antimalarial activity, to the intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof having antimalarial activity.

  本发明涉及具有抗疟疾活性的新型3'-N-取代9-去氧-9a-甲基-9a-氮杂-9a-同麦红霉素A衍生物。更具体地，本发明涉及具有抗疟疾活性的3'-N-取代9-去氧-9a-甲基-9a-氮杂-9a-同麦红霉素A和3'-N-取代3-O-去氯鼠杆菌素-9-去氧-9a-甲基-9a-氮杂-9a-同麦红霉素A衍生物，以及它们的制备中间体、制备方法、用作治疗剂的用途以及具有抗疟疾活性的盐。
• FATTY ACID MACROLIDE DERIVATIVES AND THEIR USES
  申请人：Vu Chi B.

  公开号：US20130045939A1

  公开（公告）日：2013-02-21

  The invention relates to fatty and macrolide derivatives; compositions comprising an effective amount of fatty acid macrolide derivative; and methods for treating or preventing an autoimmune disorders and diseases with inflammation as the underlying etiology comprising the administration of an effective amount of a fatty acid macrolide derivative.

  本发明涉及脂肪和大环内酯衍生物；包含有效量的脂肪酸大环内酯衍生物的组合物；以及治疗或预防自身免疫性疾病和以炎症为潜在病因的疾病的方法，其中包括给予有效量的脂肪酸大环内酯衍生物。
• Azithromycin derivatives with epithelial barrier enhancement properties
  申请人：EpiEndo Pharmaceuticals ehf

  公开号：US10723752B2

  公开（公告）日：2020-07-28

  The invention provides novel compounds that are derivatives of Azithromycin and that have been found by the current inventors to have low antimicrobial activity but significant epithelial barrier enhancement properties. The invention further provides use of the compounds as a medicament, in particular in the treatment or prophylaxis of a disease or condition that is caused by a defect in epithelial cells or tissue, or a disease or condition that benefits from enhancement or restoration of epithelial barrier function, for example diseases of the respiratory tract.

  本发明提供了新型化合物，它们是阿奇霉素的衍生物，本发明人发现它们具有较低的抗菌活性，但具有显著的上皮屏障增强特性。本发明进一步提供了这些化合物作为药物的用途，特别是用于治疗或预防由上皮细胞或组织缺陷引起的疾病或病症，或受益于上皮屏障功能增强或恢复的疾病或病症，例如呼吸道疾病。
• AZITHROMYCIN DERIVATIVES WITH EPITHELIAL BARRIER ENHANCEMENT PROPERTIES
  申请人：EpiEndo Pharmaceuticals ehf.

  公开号：EP3377511B1

  公开（公告）日：2020-05-13
• Azithromycin Derivatives With Epithelial Barrier Enhancement Properties
  申请人：EPI-ENDO Pharmaceuticals ehf

  公开号：US20180354981A1

  公开（公告）日：2018-12-13

  The invention provides novel compounds that are derivatives of Azithromycin and that have been found by the current inventors to have low antimicrobial activity but significant epithelial barrier enhancement properties. The invention further provides use of the compounds as a medicament, in particular in the treatment or prophylaxis of a disease or condition that is caused by a defect in epithelial cells or tissue, or a disease or condition that benefits from enhancement or restoration of epithelial barrier function, for example diseases of the respiratory tract.