4a-(2-amino-5-oxo-4,5-dihydro-3H-imidazol-4-yl)-2,4,4a,8-tetrahydro-2,6,8-trimethylpyrimido[5,4-e]-1,2,4-triazine-3,5,7(6H)-trione

• 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: 4a-(2-amino-5-oxo-4,5-dihydro-3H-imidazol-4-yl)-2,4,4a,8-tetrahydro-2,6,8-trimethylpyrimido[5,4-e]-1,2,4-triazine-3,5,7(6H)-trione
• 英文别名: 2096A,B；4a-(2-amino-5-oxo-1,4-dihydroimidazol-4-yl)-2,6,8-trimethyl-4H-pyrimido[5,4-e][1,2,4]triazine-3,5,7-trione
• 化学式: C₁₁H₁₄N₈O₄
• 分子量: 322.283
• InChiKey: PZTLBIWVZALOAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4a-(2-amino-5-oxo-4,5-dihydro-3H-imidazol-4-yl)-2,4,4a,8-tetrahydro-2,6,8-trimethylpyrimido[5,4-e]-1,2,4-triazine-3,5,7(6H)-trione 以 水 为溶剂， 反应 4.0h， 生成 2-氨基-3,5-二氢-4H-咪唑-4-酮 、 3,8,10-三甲基-2,3,5,8,10-五氮杂双环[4.4.0]癸-1,5-二烯-4,7,9-三酮
  参考文献：
  名称：

  Isolation of a Novel Protein Tyrosine Phosphatase Inhibitor, 2-Methyl-Fervenulone, and Its Precursors from Streptomyces

  摘要：

  High-throughput screening identified an extract from Streptomyces sp, IM 2096 with inhibitory activity toward several protein tyrosine phosphatases (PTPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this extract and their structures elucidated by interpretation of spectroscopic data and confirmed by degradation and synthesis. The novel glycocyamidine derivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, known as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor with comparable potency to vanadate. The imidazo[4,5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.

  DOI：

  10.1021/np000293+

文献信息

• Novel protein tyrosine phosphatase inhibitor
  申请人：——

  公开号：US20040138218A1

  公开（公告）日：2004-07-15

  Use of a compound of formula (I), wherein each R, which are the same or different, is H or C 1 -C 6 alkyl, and X completes a ring which is a substituted triazine having one of the following formulae (II) to (IV), wherein R′ is H or C 1 -C 6 alkyl; or an enol tautomer of a compound of formula (I) in which any of the groups R or R′ is hydrogen; in the manufacture of a medicament for use as a protein tyrosine phosphatase (PTP) inhibitor. Formula (I) embraces 2-methylfervenulone, which can be produced by fermentation of a novel microbial strain. Fermentation of the said strain also produces novel precursors to 2-methylfervenulone having utility as prodrugs. 1

  使用式 (I) 的化合物，其中每个 R（相同或不同）为 H 或 C 1 -C 6 烷基，X 构成一个环，该环是具有下式（II）至（IV）之一的取代三嗪，其中 R′是 H 或 C 1 -C 6 烷基；或式（I）化合物的烯醇同系物，其中任一基团 R 或 R′为氢；用于制造用作蛋白酪氨酸磷酸酶（PTP）抑制剂的药物。式（Ⅰ）包括 2-甲基铁酮，可通过新型微生物菌株发酵生产。上述菌株的发酵还可产生新型的 2-甲基阿魏酰前体，可用作原药。 1
• US7199121B2
  申请人：——

  公开号：US7199121B2

  公开（公告）日：2007-04-03
• [EN] NOVEL PROTEIN TYROSINE PHOSPHATASE INHIBITOR<br/>[FR] NOUVEL INHIBITEUR DE PROTEINE TYROSINE PHOSPHATASE
  申请人：INST OF MOLECUL & CELL BIOLOGY

  公开号：WO2002020525A2

  公开（公告）日：2002-03-14

  Use of a compound of formula (I), wherein each R, which are the same or different, is H or C1-C6 alkyl, and X completes a ring which is a substituted triazine having one of the following formulae (II) to (IV), wherein R' is H or C1-C6 alkyl; or an enol tautomer of a compound of formula (I) in which any of the groups R or R' is hydrogen; in the manufacture of a medicament for use as a protein tyrosine phosphatase (PTP) inhibitor. Formula (I) embraces 2-methylfervenulone, which can be produced by fermentation of a novel microbial strain. Fermentation of the said strain also produces novel precursors to 2-methylfervenulone having utility as prodrugs.