| 199188-94-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 199188-94-8
• 化学式: C₂₉H₃₈F₃NO₁₁
• 分子量: 633.616
• InChiKey: HBBQUOZHZREPTI-UZNBPBEVSA-N

物化性质

• 沸点：
  876.0±65.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.38
• 重原子数：
  44.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  189.61
• 氢给体数：
  7.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 (2R,3R,4R)-6-{Methyl-[3-phenyl-3-(4-trifluoromethyl-phenoxy)-propyl]-amino}-3-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-hexane-1,2,4,5-tetraol
  参考文献：
  名称：

  Maillard Reaction of Lactose and Fluoxetine Hydrochloride, a Secondary Amine

  摘要：

  Analysis of commercially available generic formulations of fluoxetine HCl revealed the presence of lactose as the most common excipient. We show that such formulations are inherently less stable than formulations with Starch as the diluent due to the Maillard reaction between the drug, a secondary amine hydrochloride, and lactose. The Amadori rearrangement product was isolated and characterized; the characterization was aided by reduction with sodium borohydride and subsequent characterization,of this reduced adduct. The lactose-fluoxetine HCl reaction was examined in aqueous ethanol and in the solid state, in which factors such as water content, lubricant concentration, and temperature were found to influence the degradation. N-Formylfluoxetine was identified as a major product of this Maillard reaction and it is proposed that N-formyl compounds be used as markers for this drug-excipient interaction since they are easy to prepare synthetically. Many characteristic volatile products of the Maillard reaction have been identified by GC/MS, including furaldehyde, maltol, and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one. Close similarity between the degradation products of simple mixtures and formulated generic products was found, however, at least one product decomposed at a rate nearly 10 times that predicted from the simple models. Maillard products have also been identified in unstressed capsules. The main conclusion is that drugs which are secondary amines (not just primary amines as sometimes reported) undergo the Maillard reaction with lactose under pharmaceutically relevant conditions. This finding should be considered during the selection of excipients and stability protocols for drugs which are secondary amines or their salts, just as it currently is for primary amines.

  DOI：

  10.1021/js9702067
• 作为产物：
  描述：

  盐酸氟西汀 、 乳糖 生成
  参考文献：
  名称：

  Maillard Reaction of Lactose and Fluoxetine Hydrochloride, a Secondary Amine

  摘要：

  Analysis of commercially available generic formulations of fluoxetine HCl revealed the presence of lactose as the most common excipient. We show that such formulations are inherently less stable than formulations with Starch as the diluent due to the Maillard reaction between the drug, a secondary amine hydrochloride, and lactose. The Amadori rearrangement product was isolated and characterized; the characterization was aided by reduction with sodium borohydride and subsequent characterization,of this reduced adduct. The lactose-fluoxetine HCl reaction was examined in aqueous ethanol and in the solid state, in which factors such as water content, lubricant concentration, and temperature were found to influence the degradation. N-Formylfluoxetine was identified as a major product of this Maillard reaction and it is proposed that N-formyl compounds be used as markers for this drug-excipient interaction since they are easy to prepare synthetically. Many characteristic volatile products of the Maillard reaction have been identified by GC/MS, including furaldehyde, maltol, and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one. Close similarity between the degradation products of simple mixtures and formulated generic products was found, however, at least one product decomposed at a rate nearly 10 times that predicted from the simple models. Maillard products have also been identified in unstressed capsules. The main conclusion is that drugs which are secondary amines (not just primary amines as sometimes reported) undergo the Maillard reaction with lactose under pharmaceutically relevant conditions. This finding should be considered during the selection of excipients and stability protocols for drugs which are secondary amines or their salts, just as it currently is for primary amines.

  DOI：

  10.1021/js9702067