YA5E5HR6BL | 1248590-48-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: YA5E5HR6BL
• 英文别名: 8-[[(3R,4R)-4-amino-3-hydroxypiperidin-1-yl]methyl]-5-(3-methoxyphenyl)-6H-pyrido[2,3-e][1,2,4]triazin-6-ol
• CAS: 1248590-48-8
• 化学式: C₁₉H₂₄N₆O₃
• 分子量: 384.438
• InChiKey: QKOZSBSATIOQSY-YNPPLXCJSA-N

物化性质

• 沸点：
  671.8±65.0 °C(Predicted)
• 密度：
  1.377±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

反应信息

• 作为产物：
  描述：

  (3R,4R)-4-氨基-1-[[4-[(3-甲氧基苯基)氨基]吡咯并[2,1-f][1,2,4]三嗪-5-基]甲基]哌啶-3-醇 在 nicotinamide adenine dinucleotide phosphate 作用下， 反应 1.0h， 生成 YA5E5HR6BL 、 N9XQ32Vyq7
  参考文献：
  名称：

  Mechanistic Studies on a P450-Mediated Rearrangement of BMS-690514: Conversion of a Pyrrolotriazine to a Hydroxypyridotriazine

  摘要：

  BMS-690514 ((3R,4R)-4-amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f] [1,2,4] triazin-5-yl)-methyl)-3-piperidinol) is an oral oncologic agent being developed for the treatment of patients with advanced nonsmall cell lung cancer and breast cancer. The compound is metabolized via multiple metabolic pathways, including P450-mediated oxidation at one of the carbons of its pyrrolotriazine group. Oxidation at this site results in the formation of two metabolites, M1 and M37. Mass spectrometric and NMR analysis revealed that M1 underwent an unusual structural change, where the pyrrolotriazine moiety rearranged to yield a hydroxypyridotriazine group. In contrast, the structure of the pyrrolotriazine moiety remained intact in M37. In vitro experiments with liver microsomes and deuterated or tritiated BMS-690514 containing the isotopic label on the carbon that underwent oxidation indicated that during the formation of M1, the isotope label was retained at the site of hydroxylation, while the label was lost during the formation of M37. On the basis of these results, a mechanism for the formation of M1 was proposed as follows: BMS-690514 was first oxidized by P450 enzymes either via epoxidation or an iron-oxo addition pathway to form a zwitterionic intermediate. This was followed by opening of the pyrrolotriazine ring to form an aldehyde intermediate, which could be partially trapped with methoxyamine. The aldehyde intermediate then reacted with the secondary amine of the methoxyaniline group in the molecule to form the pyridotriazine moiety of M1. This mechanism is consistent with the observed retention of the isotope label in M1. Metabolite M37 may be formed either via a common zwitterionic intermediate, shared with M1, or through a direct insertion pathway. In in vitro human liver microsome incubations, the abundance of M1 was higher than M37, suggesting that breaking of the carbon nitrogen bond to generate the aldehyde intermediate, a process similar to N-dealkylation, was a preferred pathway.

  DOI：

  10.1021/tx100337s