9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-(3-aminopropyl)-9a-homoerythromycin A | 642989-40-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-(3-aminopropyl)-9a-homoerythromycin A
• 英文别名: 3'-N-(demethyl)-3'-N-(γ-aminopropyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A；(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-[3-aminopropyl(methyl)amino]-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one
• CAS: 642989-40-0
• 化学式: C₄₀H₇₇N₃O₁₂
• 分子量: 792.064
• InChiKey: YXPCGFGVJJDSAZ-WNXQIHLLSA-N

物化性质

• 沸点：
  854.6±65.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  55
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  206
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-(3-aminopropyl)-9a-homoerythromycin A 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 5.0h， 生成 3'-N-(demethyl)-3'-N-[3-({4-[(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：

  3'-N-(demethyl)-3'-N-(β-cyanoethyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-(3-aminopropyl)-9a-homoerythromycin A
  参考文献：
  名称：

  [EN] 3'-N-SUBSTITUTED 9-DEOXO-9A-METHYL-9A-AZA-HOMOERYTHROMYCIN HAVING ANTIMALARIAL ACTIVITY
  [FR] 9-DÉOXO-9A-MÉTHYL-9A-AZAHOMOÉRYTHROMYCINE 3'-N-SUBSTITUÉE AYANT UNE ACTIVITÉ ANTIPALUDIQUE

  摘要：

  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。

  公开号：

  WO2010086351A1

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。
• Compounds, compositions and methods for treatment of inflammatory diseases and conditions
  申请人：PLIVA Pharmaceutical Industry, Incorporated

  公开号：US20040014685A1

  公开（公告）日：2004-01-22

  The present invention relates (a) to new compounds represented by Formula I: 1 wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, S represents a steroid subunit (steroid moiety) derived from steroid drug with anti-inflammatory activity and L represents a linker molecule linking M and S, (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals. Such compounds inhibit many cytokines and immune mediators involved in immune responses which cause inflammation, allergy, or alloimmunity, including without limitation IL-1, 2, 4, 5, 6, 10, 12, GMCSF, ICAM, and TNF-&agr; Importantly, anti-inflammatory steroids exert a direct anti-inflammatory effect through binding to the glucocorticosteroid receptor.

  本发明涉及以下内容：(a) 由以下式I所表示的新化合物：其中M代表来源于具有在炎症细胞中积聚特性的大环内酯亚基（大环内酯基团），S代表来源于具有抗炎活性的类固醇药物的类固醇亚基（类固醇基团），L代表连接M和S的连接分子，(b) 它们的药理学可接受的盐、前药和溶剂化物，(c) 用于它们的制备的过程和中间体，以及(d) 用于治疗人类和动物的炎症性疾病和症状。这些化合物抑制许多参与导致炎症、过敏或移植免疫反应的细胞因子和免疫介质，包括但不限于IL-1、2、4、5、6、10、12、GMCSF、ICAM和TNF-α。重要的是，抗炎类固醇通过结合糖皮质类固醇受体直接发挥抗炎作用。
• Anti-Inflammatory Macrolide Conjugates
  申请人：Mercep Mladen

  公开号：US20080096830A1

  公开（公告）日：2008-04-24

  The present invention relates (a) to new compounds represented by Formula I: wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, D represents a dibenzo[e,h]azulene subunit with anti-inflammatory, analgesic and/or antipyretic activity and L represents a linking group covalently linking M and D; (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals.

  本发明涉及(a)由式I所表示的新化合物，其中M代表源自具有在炎症细胞中积累特性的大环内酯亚基（大环内酯基团），D代表具有抗炎、镇痛和/或退热活性的二苯并[e，h]蓝亚基，L代表共价连接M和D的连接基；(b)它们的药理学可接受的盐、前药和溶剂化物，(c)制备它们的过程和中间体，以及(d)它们在治疗人类和动物的炎症性疾病和病况中的应用。
• 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。
• Modeling Cellular Pharmacokinetics of 14- and 15-Membered Macrolides with Physicochemical Properties
  作者：Višnja Stepanić、Sanja Koštrun、Ivica Malnar、Mario Hlevnjak、Kristina Butković、Irena Ćaleta、Marko Dukši、Goran Kragol、Oresta Makaruha-Stegić、Lara Mikac、Jovica Ralić、Iva Tatić、Branka Tavčar、Klara Valko、Selvira Zulfikari、Vesna Munić

  DOI：10.1021/jm101317f

  日期：2011.2.10

  Macrolides with 14- and 15-membered ring are characterized by high and extensive tissue distribution, as well as good cellular accumulation and retention. Since macrolide structures do not fit the Lipinski rule of five, macrolide pharmacokinetic properties cannot be successfully predicted by common models based on data for small molecules. Here we describe the development of the first models for macrolide cellular pharmacokinetics. By comparison of cellular accumulation and retention in six human primary cell cultures of leukocytic and lung origin, as well as in lung carcinoma cell line NCI-H292, this cell line was found to be an adequate representative cell type for modeling macrolide cellular pharmacokinetics. Accumulation and retention in the NCI-H292 cells, as well as various physicochemical properties, were determined for a set of 48 rationally designed basic macrolide compounds. Classification models for predicting macrolide cellular accumulation and retention were developed using relatively easily determined and conceptually simple descriptors: experimentally determined physicochemical parameters ChromlogD and CHI IAM, as well as a calculated number of positively charged atoms (POS). The models were further tested and improved by addition of 37 structurally diverse macrolide molecules.