Turbiak Anjanette J, Hollis Showalter H D
Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109-1065, USA.
Synthesis (Stuttg). 2010 Apr 20;41(16):i. doi: 10.1002/chin.201016160.
A new route to substituted pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones is outlined. The synthesis proceeds via pre-formed hydrazone intermediates, which are then condensed with an activated chlorouracil to build up the entire molecular framework, followed by a reductive ring closure to provide the parent series. The route has been extended to the isomeric pyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-dione class via the use of methylhydrazine as hydrazine surrogate, followed by regiospecific alkylation of the N(8)-H pyrimidotriazinediones with a range of alkyl and alkaryl substituents. This new methodology permits the generation of a wide range of compounds with variable substitution at the N(1), C(3), and N(8) positions for a heterocyclic scaffold with demonstrated pharmacological activity.
概述了一种合成取代嘧啶并[5,4 - e]-1,2,4 - 三嗪 - 5,7(1H,6H)-二酮的新方法。该合成过程通过预先形成的腙中间体进行，然后将其与活化的氯尿嘧啶缩合以构建整个分子骨架，接着进行还原环化反应以得到母体系列。通过使用甲基肼作为肼替代物，该方法已扩展至异构的嘧啶并[5,4 - e]-1,2,4 - 三嗪 - 5,7(6H,8H)-二酮类，随后用一系列烷基和芳烷基取代基对N(8)-H嘧啶并三嗪二酮进行区域特异性烷基化。这种新方法能够生成一系列在N(1)、C(3)和N(8)位置具有可变取代的化合物，用于具有已证实药理活性的杂环骨架。
