Synthesis Of The NO-releasing 2-Phenylaminopyrimidine Derivatives

2-phenylaminopyrimidine, which is one class of effective ATP-competitive inhibitors of protein tyrosine kinases(PTKs), play an important action in molecular target-directed anti-cancer therapy. Nitric oxide (NO), an important biological messenger and effector molecule, is involved in tumour immune rejection through dericted or indirected action, especially NO can reduce the production of ATP and facilitate the consumption of ATP, show synergistic action with 2-phenylaminopyrimi- dine in the mechanism of anti-cancer action. The purpose of this paper is to synthesize a kind of new 2-phenylaminopyrimidine derivates with potential double-acting anticancer activity through introducing NO donors into the structure of the lead compound of 2-phenylaminopyrimidine.We choose N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidine-amine as the lead compound of 2-phenylaminopyrimidine, Furoxan NO donors as the side chain modified group, synthesize 8 newly NO releasing-2-phenylaminopyrimidine derivates through combining those two groups by N-alkylation. We synthesized the lead compound of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidine-amine by 4 steps and optimized the technic of the synthesis by testing; meanwhile optimized the synthesis of side chain NO donors by orthogonal experiment; combined those groups in two steps and investigated different catalysts and acid absorbents.At last we synthesized 8 new compounds through experiments, the validity of their structures were determined by 1H-NMR, MS, IR.