Exploring 4,7-Disubstituted Pyrimido[4,5-d]pyrimidines as Antiviral and Anticancer Agents

Thirteen new 4,7-disubstituted pyrimido[4,5-<i>d</i>]pyrimidines were synthesized via a straightforward methodology starting from thiourea. The anti-proliferative activity of these compounds was evaluated across a diverse panel of eight cancer cell lines, with derivatives <b>7d</b> and <b>7h</b> showing efficacy against several hematological cancer types. Furthermore, all compounds were assessed for their antiviral potency against a panel of viruses. Compounds featuring a cyclopropylamino group and an aminoindane moiety exhibited remarkable efficacy against human coronavirus 229E (HCoV-229E). These findings highlight the pyrimidino[4,5-<i>d</i>]pyrimidine scaffold as an interesting framework for the design of novel antiviral agents against HCoVs, with compounds <b>7a</b>, <b>7b</b>, and <b>7f</b> emerging as strong candidates for further investigation.