Synthesis And Free Radical Scavenging Activity Of Triaminopyridine Derivatives

Radioprotective agents have been used to reduce morbidity or mortality produced by ionizing irradiation. The concept that biological systems can be protected from lethal doses of ionizing radiation by chemicals first became established in 1948. So far, the developments of chemical radioprotective agents mainly focused on aminothiols derivatives, heterocyclic compounds containing sulfur and metal complexing compounds. And a variety of substances have shown some effect in preventing radiation damage to living cells. One of them is amifostine which has come into the market as clinical medication in many countries since the late 20th century. In this paper, it is studied that amifostine and flupiritine combinate on the basis of combination principle. And the mechanisms of radiation injury and action of radioprotective agents are also summarized. Furthermore, the chemical radioprotective agents of potentially clinical application in the past 63 years are reviewed.Starting from 2,6-dichloropyrdine-3-nitropyridine, ten phosphorothioates or thiols derivative containing 2,3,6-triaminopyridine moiety were obtained via nucleophilic substitution, bromination, hydrogenated reduction, cyclization, acylation reaction and so on. Compound V was synthetized via four steps, and total yield was 27.25%; CompoundⅦwas synthetized via six steps, and total yield was 26.40%; Compound X was synthetized via six steps, and total yield was 10.92%; CompoundⅫwas synthetized via seven steps, and total yield'was 10.47%; CompoundⅩⅢ-1,ⅩⅢ-2 andⅩⅢ-3 were synthetized via four steps, and total yield was 40.89%,39.03% and 43.07% respectively; Compound XVI was synthetized via one steps, and yield was 74.46%; Compound XIX was synthetized via three steps, and total yield was 36.77%; Compound XXI was synthetized via six steps, and total yield was 37.12%. The structure of all compounds were established by 1H-NMR, 31P-NMR and MS spectra.The IC50 of free radical scavenging activities are 56,56,42,49,82,72,69,90 and 56 ug/mL for compoundsⅦ,Ⅸ-1,Ⅹ,Ⅺ-1,ⅩⅢ-1,ⅩⅢ-2,ⅩⅢ-3,ⅪⅨandⅩⅪrespectively. Their free radical scavenging activities are all higher than flupritine (ICso=94μ/mL). And the most potent compound is the X with an antiradical effect (ICso=42μg/mL) higher than ascorbic acid (IC5o=42μg/mL).In this paper, a new orgnic preparation method of reduction of nitro group was studied. Not only nitro group can be reduced, but also the bromide in aliphatic hydrocarbon can not be off at the same time via raney nickle hydrogenation reduction in room-temperature and low H2 pressure.