9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-[3-(octanoylamino)propyl]-9a-homoerythromycin A | 1262866-19-2

• 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-(octanoylamino)propyl]-9a-homoerythromycin A
• 英文别名: 3'-N-demethyl-3'-N-[3-(octanoylamino)propyl]azithromycin；3'-N-demethyl-30-N-[3-(octanoylamino)propyl]azithromycin；N-[3-[[(2S,3R,4S,6R)-2-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-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-15-oxo-1-oxa-6-azacyclopentadec-11-yl]oxy]-3-hydroxy-6-methyloxan-4-yl]-methylamino]propyl]octanamide
• CAS: 1262866-19-2
• 化学式: C₄₈H₉₁N₃O₁₃
• 分子量: 918.263
• InChiKey: LEUVODHJAMARCA-KCTFSAEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  64
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-(3-aminopropyl)-9a-homoerythromycin A 、 辛酸 在 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 四氢呋喃 为溶剂， 生成 9-deoxo-9a-aza-9a-methyl-3'-N-demethyl-3'-N-[3-(octanoylamino)propyl]-9a-homoerythromycin A
  参考文献：
  名称：

  Modeling Cellular Pharmacokinetics of 14- and 15-Membered Macrolides with Physicochemical Properties

  摘要：

  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.

  DOI：

  10.1021/jm101317f

文献信息

• 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.