2-amino-4-(dimethylamino)-7-methyl-5,7-dihydro-6H-[1,3,5]triazepin-6-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-amino-4-(dimethylamino)-7-methyl-5,7-dihydro-6H-[1,3,5]triazepin-6-one
• 英文别名: 2-amino-4-dimethylamino-7-methyl-5,7-dihydro(1,3,5)triazepin-6-one；2-Amino-4-(dimethylamino)-7-methyl-5,7-dihydro-6h-[1,3,5]triazepine-6-one；4-amino-2-(dimethylamino)-6-methyl-1,6-dihydro-1,3,5-triazepin-7-one
• 化学式: C₇H₁₃N₅O
• 分子量: 183.213
• InChiKey: KFMNBNFMKWDVOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  83.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  二甲双胍 、 丙酮醛 以50%的产率得到2-amino-4-(dimethylamino)-7-methyl-5,7-dihydro-6H-[1,3,5]triazepin-6-one
  参考文献：
  名称：

  Reaction of metformin with dicarbonyl compounds. possible implication in the inhibition of advanced glycation end product formation

  摘要：

  Dicarbonyl compounds such as methylglyoxal and glyoxal are extremely reactive glycating agents involved in the formation of advanced glycation end products (AGEs), which in turn are associated with diabetic vascular complications. Guanidino compounds such as aminoguanidine appear to inhibit AGE formation by reacting with alpha-dicarbonyl compounds. The aim of this work was to study whether the antihyperglycemic agent metformin (a guanidine-like compound) might react with reactive alpha-dicarbonyls. Metformin was incubated at pH 7.4 and 37 degrees in the presence of either methylglyoxal or glyoxal and reaction products analysed by HPLC coupled to mass tandem spectrometry. AGE formation on albumin by methylglyoxal and glyoxal in the presence or absence of metformin was also studied by measuring the fluorescence at 370/440 nm after albumin-AGE isolation by ultrafiltration. As a standard for mass spectra analysis, a metformin-methylglyoxal adduct was chemically synthesised and characterised as a triazepinone (2-amino-4-(dimethylamino)-7-methyl-5,7-dihydro-6H-[1,3,5]triazepin-6-one). The results obtained showed that metformin strongly reacted with methylglyoxal and glyoxal, forming original guanidine-dicarbonyl adducts. Reaction kinetic studies as well as mass fragmentation spectra of the reaction products were compatible with the presence of triazepinone derivatives. In the presence of metformin, AGE-related fluorescence after albumin incubation with either glyoxal or methylglyoxal was decreased by 37% and 45%, respectively. These results suggest that besides its known antihyperglycemic effect, metformin could also decrease AGE formation by reacting with alpha-dicarbonyl compounds. This is relevant to a potential clinical use of metformin in the prevention of diabetic complications by inhibition of carbonyl stress. BIOCHEM PHARMACOL 58;11:1765-1773, 1999. (C) 1999 Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(99)00263-4

文献信息

• TRIAZEPINONES, PROCESS FOR THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
  申请人：MERCK PATENT GmbH

  公开号：EP1047668A1

  公开（公告）日：2000-11-02
• US6258804B1
  申请人：——

  公开号：US6258804B1

  公开（公告）日：2001-07-10
• [EN] TRIAZEPINONES, PROCESS FOR THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION<br/>[FR] TRIAZEPINONES, PROCEDE POUR LEUR PREPARATION ET LEUR APPLICATION THERAPEUTIQUE
  申请人：MERCK PATENT GMBH

  公开号：WO1999036396A1

  公开（公告）日：1999-07-22

  (EN) The invention relates to compounds of general formula (I) which find an application in the treatment of diabetes.(FR) Cette invention se rapporte à des composés représentés par la formule générale (I), qui trouvent une application dans le traitement du diabète.
• Reaction of metformin with dicarbonyl compounds. possible implication in the inhibition of advanced glycation end product formation
  作者：Daniel Ruggiero-Lopez、Marc Lecomte、Gérard Moinet、Gérard Patereau、Michel Lagarde、Nicolas Wiernsperger

  DOI：10.1016/s0006-2952(99)00263-4

  日期：1999.12

  Dicarbonyl compounds such as methylglyoxal and glyoxal are extremely reactive glycating agents involved in the formation of advanced glycation end products (AGEs), which in turn are associated with diabetic vascular complications. Guanidino compounds such as aminoguanidine appear to inhibit AGE formation by reacting with alpha-dicarbonyl compounds. The aim of this work was to study whether the antihyperglycemic agent metformin (a guanidine-like compound) might react with reactive alpha-dicarbonyls. Metformin was incubated at pH 7.4 and 37 degrees in the presence of either methylglyoxal or glyoxal and reaction products analysed by HPLC coupled to mass tandem spectrometry. AGE formation on albumin by methylglyoxal and glyoxal in the presence or absence of metformin was also studied by measuring the fluorescence at 370/440 nm after albumin-AGE isolation by ultrafiltration. As a standard for mass spectra analysis, a metformin-methylglyoxal adduct was chemically synthesised and characterised as a triazepinone (2-amino-4-(dimethylamino)-7-methyl-5,7-dihydro-6H-[1,3,5]triazepin-6-one). The results obtained showed that metformin strongly reacted with methylglyoxal and glyoxal, forming original guanidine-dicarbonyl adducts. Reaction kinetic studies as well as mass fragmentation spectra of the reaction products were compatible with the presence of triazepinone derivatives. In the presence of metformin, AGE-related fluorescence after albumin incubation with either glyoxal or methylglyoxal was decreased by 37% and 45%, respectively. These results suggest that besides its known antihyperglycemic effect, metformin could also decrease AGE formation by reacting with alpha-dicarbonyl compounds. This is relevant to a potential clinical use of metformin in the prevention of diabetic complications by inhibition of carbonyl stress. BIOCHEM PHARMACOL 58;11:1765-1773, 1999. (C) 1999 Elsevier Science Inc.