4-二甲基氨基-5-(羟基甲基)-1-甲基-2-苯基吡唑-3-酮 | 13097-17-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-二甲基氨基-5-(羟基甲基)-1-甲基-2-苯基吡唑-3-酮
• 英文名称: 4-dimethylamino-3-hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-one
• 英文别名: 3-Hydroxymethyl-2-methyl-4-dimethylamino-1-phenyl-Δ³-pyrazolin-5-on；3-Hydroxymethyl-2-methyl-4-dimethylamino-1-phenyl-3-pyrazol-5-on；4-dimethylamino-5-hydroxymethyl-1-methyl-2-phenyl-1,2-dihydro-pyrazol-3-one；3-Hydroxymethylaminopyrine；4-(dimethylamino)-5-(hydroxymethyl)-1-methyl-2-phenylpyrazol-3-one
• CAS: 13097-17-1
• 化学式: C₁₃H₁₇N₃O₂
• 分子量: 247.297
• InChiKey: BATBESUQPUOBOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  4-二甲基氨基-5-(羟基甲基)-1-甲基-2-苯基吡唑-3-酮 在 氘氧化钠 作用下， 反应 6.0h， 以150 mg的产率得到4-dimethylamino-3-dideuterohydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-one
  参考文献：
  名称：

  使用稳定的同位素示踪技术对大鼠和人体中氨基比林的代谢研究。

  摘要：

  The metabolites of aminopyrine (AM) were analyzed by using stable isotope tracer techniques. After the oral administration of an equimolar mixture of AM and AM-2-CD3 (mixture 1), or an equimolar mixture of AM-3-CH2OH and AM-3-CD2OH (mixture 2), or either AM-3-CD3 or AM-4-N (CD3)2 to rats, the urinary metabolites were extracted with chloroform at pH 7.0, and the extracts were subjected to gas chromatography-mass spectrometry after trimethylsilylation. Characteristic doublet peaks in the mass spectra indicated the presence of a metabolite originating from mixture 1 or 2 mentioned above. The new metabolites detected by gas chromatography-mass spectrometry (GC-MS) were identified as 3-hydroxymethyl-4-monomethylaminoantipyrine (MAA-3-CH2OH) and 3-hydroxymethyl-4-aminoantipyrine (AA-3-CH2OH) from the shifts of the mass numbers of the molecular ions after the administration of AM-3-CD3 and AM-4-N(CD3)2. Two other metabolites were newly detected following the administration of mixture 2(AM-3-CH2OH is an intermediary metabolite of AM) to rats. They were identified as 3-hydroxymethyl-4-acetylaminoantipyrine (AcMAA-3-CH2OH) and 3-hydroxymethyl-4-acetylaminoantipyrine (AcAA-3-CH2OH). MAA-3-CH2OH was also detected in human urine after the oral administration of AM.

  DOI：

  10.1248/cpb.29.1724

文献信息

• Use of synthetic metalloporphyrins for preparation and prediction of
  申请人：Abbott Laboratories

  公开号：US05760216A1

  公开（公告）日：1998-06-02

  A method for the systematic and efficient synthetic preparation and identification of metabolites of a pharmaceutical product in order to study possible toxic and/or otherwise biologically-active metabolites of such pharmaceutical products as early and conveniently as possible in the very expensive drug development process, comprising adding samples of the pharmaceutical product to a series of combinations of a synthetic metalloporphyrin (SMP) with a synthetic metalloporphyrin-co-oxidizing reagent in the presence of a suitable solvent, under specified conditions, in a manner such that each sample of pharmaceutical product is reacted with a different combination of synthetic metalloporphyrin, SMP-co-oxidizing reagent and solvent, followed by separation and isolation of the resulting oxidative products, then confirmation of the identity of metabolites from the pre-identified oxidative products by appropriate animal model studies, and subjecting the actual metabolites prepared in larger quantities by the above method to toxicologic, pathologic, histopathologic, mechanistic or genotoxic testing in order to identify toxic and/or otherwise metabolically-active beneficial or detrimental individual metabolites.

  一种系统和高效的合成制备和鉴定药物代谢物的方法，旨在在非常昂贵的药物开发过程中，尽早便捷地研究可能的有毒和/或其他生物活性代谢物。该方法包括将药物产品样品加入一系列合成金属卟啉（SMP）和合成金属卟啉-氧化试剂的组合中，在适当的溶剂存在下，按照规定条件进行反应，使每个药物产品样品与不同的合成金属卟啉、SMP-氧化试剂和溶剂的组合反应，然后分离和分离所得的氧化产物，接着通过适当的动物模型研究确认代谢物的身份，最后将通过上述方法制备的实际代谢物进行毒理学、病理学、组织病理学、机制或基因毒性测试，以确定有毒和/或其他代谢活性有益或有害的个体代谢物。
• USE OF SYNTHETIC METALLOPORPHYRINS FOR PREPARATION AND PREDICTION OF DRUG METABOLITES
  申请人：Abbott Laboratories

  公开号：EP0781261A2

  公开（公告）日：1997-07-02
• US5760216A
  申请人：——

  公开号：US5760216A

  公开（公告）日：1998-06-02
• [EN] USE OF SYNTHETIC METALLOPORPHYRINS FOR PREPARATION AND PREDICTION OF DRUG METABOLITES<br/>[FR] UTILISATION DE METALLOPORPHYRINES SYNTHETIQUES POUR LA PREPARATION DE METABOLITES ET L'IDENTIFICATION PRECOCE DE LEURS CARACTERISTIQUES DANS LES MEDICAMENTS
  申请人：——

  公开号：WO1996008455A2

  公开（公告）日：1996-03-21

  [EN] A method for the systematic and efficient synthetic preparation and identification of metabolites of a pharmaceutical product in order to study possible toxic and/or otherwise biologically-active metabolites of such pharmaceutical products as early and conveniently as possible in the very expensive drug development process, comprising adding samples of the pharmaceutical product to a series of combinations of a synthetic metalloporphyrin (SMP) with a synthetic metalloporphyrin-co-oxidizing reagent in the presence of a suitable solvent, under specified conditions, in a manner such that each sample of pharmaceutical product is reacted with a different combination of synthetic metalloporphyrin, SMP-co-oxidizing reagent and solvent, followed by separation and isolation of the resulting oxidative products, then confirmation of the identity of metabolites from the pre-identified oxidative products by appropriate animal model studies, and subjecting the actual metabolites prepared in larger quantities by the above method to toxicologic, pathologic, histopathologic, mechanistic or genotoxic testing in order to identify toxic and/or otherwise metabolically-active beneficial or detrimental individual metabolites.
  [FR] Procédé de préparation et d'identification systématique efficiente de métabolites synthétiques d'un produit pharmaceutique, dans le but d'étudier les éventuels métabolites toxiques et/ou biologiquement actifs contenus dans ces produits pharmaceutiques à une étape aussi précoce que possible au cours du processus de développement de médicaments, qui est extrêmement coûteux. Ce procédé consiste à ajouter des échantillons du produit pharmaceutique à une série de combinaisons d'une métalloporphyrine synthétique (SMP) avec un réactif co-oxydant la métalloporphyrine synthétique, en présence d'un solvant approprié, dans des conditions spécifiées, de sorte que chaque échantillon du produit pharmaceutique réagit avec une différente combinaison de métalloporphyrine synthétique, réactif co-oxydant la SMP et solvant, cette étape étant suivie d'une étape de séparation et d'isolation des produits résultant de l'oxydation, puis d'une étape de confirmation de l'identité des métabolites parmi les produits préidentifiés résultant de l'oxydation, se fondant sur des études effectuées sur des modèles animaux appropriés. Finalement, on soumet les métabolites produits en grandes quantités par le procédé ci-décrit à des tests toxicologiques, pathologiques, histopathologiques, mécanistes ou génotoxiques, afin d'identifier des métabolites individuels toxiques et/ou agissant sur le métabolisme, bénéfiques ou nuisibles.
• Metabolic studies of aminopyrine in rat and man by using stable isotope tracer techniques.
  作者：TSUYOSHI GOROMARU、TAKASHI FURUTA、SHIGEO BABA、ATSUKO NODA、SADAO IGUCHI

  DOI：10.1248/cpb.29.1724

  日期：——

  The metabolites of aminopyrine (AM) were analyzed by using stable isotope tracer techniques. After the oral administration of an equimolar mixture of AM and AM-2-CD3 (mixture 1), or an equimolar mixture of AM-3-CH2OH and AM-3-CD2OH (mixture 2), or either AM-3-CD3 or AM-4-N (CD3)2 to rats, the urinary metabolites were extracted with chloroform at pH 7.0, and the extracts were subjected to gas chromatography-mass spectrometry after trimethylsilylation. Characteristic doublet peaks in the mass spectra indicated the presence of a metabolite originating from mixture 1 or 2 mentioned above. The new metabolites detected by gas chromatography-mass spectrometry (GC-MS) were identified as 3-hydroxymethyl-4-monomethylaminoantipyrine (MAA-3-CH2OH) and 3-hydroxymethyl-4-aminoantipyrine (AA-3-CH2OH) from the shifts of the mass numbers of the molecular ions after the administration of AM-3-CD3 and AM-4-N(CD3)2. Two other metabolites were newly detected following the administration of mixture 2(AM-3-CH2OH is an intermediary metabolite of AM) to rats. They were identified as 3-hydroxymethyl-4-acetylaminoantipyrine (AcMAA-3-CH2OH) and 3-hydroxymethyl-4-acetylaminoantipyrine (AcAA-3-CH2OH). MAA-3-CH2OH was also detected in human urine after the oral administration of AM.