Synthesis of new 9-(4´-RO-phenyl)-6-cyanopurine derivatives

Abstract

Cancer remains to be one of the leading causes of death worldwide of which the scientific community continuously struggles to combat on a daily basis [1]. In developed countries, colorectal cancer is one of the most frequent types of cancer where busy and stressful lifestyles contribute to diets rich in unhealthy fats which can be a preliminary cause of this cancer [2]. Unfortunately, there is not a concrete cure for this cancer and not all patients respond equally to the administered drugs [3]. Some even develop tumor resistance upon the intake of their therapeutic drugs due to the tumors’ different genetic profiles [3]. The ineffective treatment in many patients causes thousands of annual casualties which stimulated further research in prospect of novel anticancer drugs [1]. Recently, in our research group, the pyrimido[5,4-d]pyrimidines of general structure 1 (Figure 1) were identified as a new class of heterocyclic compounds active against HCT116 (p-53wt) colon cancer cells. The biological results showed that the activity depends on the substituents R and R1 that decorate the heterocycle. The synthetic strategy developed in our research group to generate the pyrimidopyrimidine ring has the 9-substitutedpurines as crucial intermediates [5, 6, 7], that are not available commercially. Herein, we describe the synthesis of new 9-substitutedpurine derivatives that will be used as starting reagents to synthesize new pyrimido[5,4-d]pyrimidines.