NAD+-dependent DNA ligase inhibitors

摘要

Disclosed herein are pyrido[2,3-d]pyrimidines having the structure wherein R₁, and R₂ are independently selected from nitro and amino; wherein R₃ is selected from alkyl (C1-C10) and cycloalkyl (C3-C8); wherein R₄ is selected from hydrogen, benzyl, alkyl (C1-C10), cycloalkyl (C3-C8), arylalkyl (C4-C8), and aryl (C3-C8); wherein R₅ and R₆ are independently selected from hydrogen, benzyl, alkyl (C1-C10), cycloalkyl (C3-C8), arylalkyl (C4-C14), and aryl (C3-C8); wherein R₃ and R₄ may form a ring; wherein R₅ and R₆ may form a ring or a heterocyclic structure; and wherein R₅ and R₆ are independently unsubstituted or substituted, wherein each substituent is independently selected from halogen, amino, alkyl (C1-C6), haloalkyl (C1-C6), alkoxy(C1-C6), alkylenedioxy, aryl, heteroaryl, and cycloalkyl (C3-C8). Also disclosed are methods for the preparation of compounds of Formula I and various intermediates. These compounds are useful as NAD+-dependent DNA ligase inhibitors.