1-Butyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione | 164520-07-4

• 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: 1-Butyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione
• 英文别名: 1-butyl-6-methyl-3-phenylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione；1-butyl-6-methyl-3-phenylpyrimido[5,4-e][1,2,4]triazine-5,7-dione
• CAS: 164520-07-4
• 化学式: C₁₆H₁₇N₅O₂
• 分子量: 311.343
• InChiKey: VMOXVOYAWMHYEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  77.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-Butyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 6-Methyl-3-phenyl-1-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione
  参考文献：
  名称：

  Facile and General Syntheses of 1-Alkyltoxoflavin and 8-Alkylfervenulin Derivatives of Biological Significance by the Regiospecific Alkylation of Reumycin (1-Demethyltoxoflavin, 8-Demethylfervenulin) Derivatives

  摘要：

  Regiospecific alkylation of reumycins (6) under alkaline conditions with a dialkyl sulfate or alkyl halide in dioxane and in DMF to provide 1-alkyltoxoflavins (5) of biological significance and 8-alkylfervenulins (7), respectively, is described.

  DOI：

  10.3987/com-97-7750
• 作为产物：
  描述：

  1-Cyclopentyl-6-methyl-3-phenylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione 在 potassium carbonate 、 正丁胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 1-Butyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione
  参考文献：
  名称：

  Facile and General Syntheses of 1-Alkyltoxoflavin and 8-Alkylfervenulin Derivatives of Biological Significance by the Regiospecific Alkylation of Reumycin (1-Demethyltoxoflavin, 8-Demethylfervenulin) Derivatives

  摘要：

  Regiospecific alkylation of reumycins (6) under alkaline conditions with a dialkyl sulfate or alkyl halide in dioxane and in DMF to provide 1-alkyltoxoflavins (5) of biological significance and 8-alkylfervenulins (7), respectively, is described.

  DOI：

  10.3987/com-97-7750

文献信息

• General syntheses of 1-alkyltoxoflavin and 8-alkylfervenulin derivatives of biological significance by the regioselective alkylation of reumycin derivatives and the rates of transalkylation from 1-alkyltoxoflavins into nucleophiles
  作者：Tomohisa Nagamatsu、Hirofumi Yamasaki

  DOI：10.1039/b007302o

  日期：——

  Regioselective alkylations of reumycin derivatives under alkaline conditions with a dialkyl sulfate or alkyl halide in 1,4-dioxane or DMF to provide 1-alkyltoxoflavin or 8-alkylfervenulin derivatives of biological significance, are described. Namely, the primary and secondary alkylations of reumycin derivatives with appropriate dialkyl sulfates or alkyl bromides under alkaline conditions in 1,4-dioxane gave predominantly 1-alkyltoxoflavin derivatives, while the same alkylations in DMF instead of 1,4-dioxane gave predominantly 8-alkylfervenulin derivatives. In the case of tertiary alkylation, the reumycin derivative with 2-bromo-2-methylpropane in both solvents under the same conditions yielded only the 1-alkyltoxoflavin derivative. Moreover, the rates of transalkylation from 1-alkyltoxoflavin derivatives into nucleophiles, e.g. DMF and n-butylamine, are also described. That is, the toxoflavin derivatives possessing a primary alkyl group at the 1-position were easily dealkylated from the 1-position by heating with DMF, whereupon reumycin (i.e., 1-dealkyltoxoflavin, 8-dealkylfervenulin) derivatives were formed. In other words, transalkylation from the toxoflavin derivatives into DMF took place. However, the transalkylation of 1-alkyltoxoflavin derivatives possessing a secondary or tertiary alkyl group at the 1-position was not observed under such conditions. On the other hand, when heating 1-alkyltoxoflavin derivatives with n-butylamine in 1,4-dioxane, the transalkylations were more easily observed even in the case of 1-alkyltoxoflavin derivatives substituted by a tertiary alkyl group.

  在碱性条件下，使用二烷基硫酸酯或烷基卤化物在1,4-二恶烷或DMF中对reumycin衍生物进行区域选择性烷基化，生成具有生物学意义的1-烷基toxoflavin或8-烷基fervenulin衍生物，本文对此进行了描述。即，在碱性条件下，使用适当的二烷基硫酸酯或烷基溴化物在1,4-二恶烷中对reumycin衍生物进行伯和仲烷基化，主要生成1-烷基toxoflavin衍生物，而在DMF中替代1,4-二恶烷进行同样的烷基化，则主要生成8-烷基fervenulin衍生物。在叔烷基化的情况下，在相同条件下，使用2-溴-2-甲基丙烷在两种溶剂中的reumycin衍生物仅生成1-烷基toxoflavin衍生物。此外，还描述了从1-烷基toxoflavin衍生物向亲核试剂（例如DMF和正丁胺）的转移烷基化速率。也就是说，在1-位具有伯烷基的toxoflavin衍生物通过与DMF加热容易从1-位去烷基化，随后形成reumycin（即1-去烷基toxoflavin，8-去烷基fervenulin）衍生物。换言之，从toxoflavin衍生物向DMF发生了转移烷基化。然而，在1-位具有仲或叔烷基的1-烷基toxoflavin衍生物的转移烷基化在这些条件下未被观察到。另一方面，当在1,4-二恶烷中加热1-烷基toxoflavin衍生物与正丁胺时，即使在1-位上被叔烷基取代的1-烷基toxoflavin衍生物的情况下，转移烷基化也更容易被观察到。
• Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives as novel small molecule chaperone amplifiers
  作者：Yuefen Zhou、Linyi Wei、Thomas P. Brady、P.S. Murali Mohan Redddy、Tram Nguyen、Jinhua Chen、Qingyan Au、Il Sang Yoon、Gary Yip、Bin Zhang、Jack R. Barber、Shi Chung Ng

  DOI：10.1016/j.bmcl.2009.05.073

  日期：2009.8

  Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC50 = 2.5 μM) and significant cytoprotection in both rotenone (EC50 = 0.23 μM) and oxygen-glucose deprivation cell toxicity

  嘧啶[5,4- e ] [1,2,4]三嗪-5,7（1 H，6 H）-二酮衍生物被研究为热休克因子1转录活性的新型小分子放大器。铅的优化导致化合物4A-13的发现，该化合物在轻度热应激下（EC 50  = 2.5μM）表现出强大的HSF1活性，在鱼藤酮（EC 50  = 0.23μM）和氧-葡萄糖剥夺细胞毒性模型中均具有显着的细胞保护作用（在2.5μM时具有80％的保护）。
• Pyrimido[5,4-e][1,2,4]triazine-5,7-diones, processes for preparing them and their use
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US20040242583A1

  公开（公告）日：2004-12-02

  The invention relates to pyrimido[5,4-e][1,2,4]triazine-5,7-diones, pharmaceutically acceptable salts thereof and physiologically functional derivatives. The invention therefore relates to compounds of the formula I, 1 in which the radicals have the given meanings, and to their physiologically tolerated salts and processes for preparing them. The compounds are suitable for use as antidiabetics, for example.

  本发明涉及嘧啶并[5,4-e][1,2,4]三嗪-5,7-二酮、其医药上可接受的盐和生理功能衍生物。因此，本发明涉及公式I中的化合物，其中基团具有给定的含义，并涉及其生理耐受的盐和制备它们的方法。这些化合物适用于例如作为抗糖尿病药物。
• Pyrimido[5,4-e][1,2,4]triazine-5-7-diones, processes for preparing them and their use
  申请人：Sanofi-Aventis Deutschland GmbH

  公开号：US07737144B2

  公开（公告）日：2010-06-15

  The invention relates to pyrimido[5,4-e][1,2,4]triazine-5,7-diones, pharmaceutically acceptable salts thereof and physiologically functional derivatives. The invention therefore relates to compounds of the formula I, in which the radicals have the given meanings, and to their physiologically tolerated salts and processes for preparing them. The compounds are suitable for use as antidiabetics, for example.

  该发明涉及嘧啶并[5,4-e][1,2,4]三嗪-5,7-二酮、其药学上可接受的盐和生理功能衍生物。因此，该发明涉及式I的化合物，其中基团具有给定的含义，以及它们的生理耐受盐和制备它们的过程。这些化合物适用于例如作为抗糖尿病药物。
• PYRIMIDO 5,4-e 1,2,4 TRIAZIN-5,7-DIONE, VERF AHREN ZU DEREN HERSTELLUNG UND DEREN VERWENDUNG
  申请人：Sanofi-Aventis Deutschland GmbH

  公开号：EP1587806B1

  公开（公告）日：2008-11-12