Efficient Two-Step Synthesis of Novel Pyrimido[4,5-<i>d</i>] Pyrimidines with Potent Neuroprotective, Antioxidant, and A<i>β</i> Anti-Aggregation Properties

Abstract

Eleven new differently substituted N,7-diphenylpyrimido [4,5-d]pyrimidin-4-amines 4a–k were synthesized from readily available reagents in a simple and inexpensive two-step procedure with yields up to 57%. Neuroprotective analysis against H2O2 and analysis using ORAC assays identified compounds 4g, 4i and 4j as promising antioxidant compounds. These compounds also showed potent inhibition of Aβ1–42 self-aggregation, and suitable physicochemical properties predicted by Datawarior software V6.1.0, this biological activity and physicochemical property being of great interest for pathologies linked to oxidative stress, such as Alzheimer’s disease.

Keywords

• A<i>β</i>_1-42 self-aggregation inhibition
• antioxidant
• neuroprotective agents
• pyrimido [4,5-<i>d</i>] pyrimidines