Biological Evaluation of Pyrimidopyrimidines as Multi-Targeted Small Molecule Inhibitors and Resistance Modifying Agents

Advances in the chemical and biological diversity of heterocyclic systems incorporating pyrimido[1,6-a]pyrimidine and pyrimido[1,6-c]pyrimidine scaffolds

“…Accordingly, there are two possible pathways (A and B) for the cyclization step of compounds 53 to afford the pyrimido [1,6-c]quinazolines (54). In route A, 1,3 proton transfer generates the tautomer 55. The carbon at position 2 of the pyrimidine ring is attacked by the hydrogen anion produced from sodium borohydride to form the intermediate 56. and nally, 1,3 proton transfer yields the products 54.…”

“…In route A, 1,3 proton transfer generates the tautomer 55. The carbon at position 2 of the pyrimidine ring is attacked by the hydrogen anion produced from sodium borohydride to form the intermediate 56. and nally, 1,3 proton transfer yields the products 54. 62 In the same way, pyrimido[1,6-c]quinazoline (61) was synthesized with a yield of 50% by treatment of N-methylpyrimidine 60 with NaBH 4 /MeOH at room temperature.…”

“…Due to their various substantial biological characteristics, pyrimidopyrimidine compounds have recently established a notable place in the work of researchers in the eld of medicinal chemistry. 1 Pyrimido [4,5-d]pyrimidines are used as cancer cell growth inhibitors, 2 antioxidants, 3 agents to reduce dihydrofolic acid to tetrahydrofolic acid, 4 antidiabetics, 5 angiogenesis inhibitors, 6 resistance modication agents, 7 Mycobacterium tuberculosis, 8 hypertension, 9 and allergy symptom treatments, 10 antibacterial 11 and antiviral agents, 12 antitumor agents that inhibit monocarboxylate transporters (MCTs), [13][14][15] anti-inammatory 16 and hepatoprotective agents, 17 and tyrosine kinase inhibitors. 18 The pyrimidopyrimidines of this class comprise 4H-pyrimido [1,6-a]pyrimidine, 6H-pyrimido [1,6-a]-pyrimidine, and 1H-pyrimido [1,6-c]pyrimidine ( Fig.…”