Synthesis and Activity of Novel 5‐Substituted Pyrrolo[2,3‐ d ]pyrimidine Analogues as pp60 c‐Src Tyrosine Kinase Inhibitors

Therapy with receptor tyrosine kinase inhibitors provides an improved treatment option in a number of diseases such as cancer, myocardial infection, osteoporosis, stroke, and neurodegeneration. We have designed, synthesized, and evaluated a series of novel 2‐amino‐5‐[(benzyl)imino]methyl‐3,7‐dihydro‐4 H ‐pyrrolo[2,3‐ d ]pyrimidine‐4‐one 7a and 2‐amino‐5‐[(substituted‐benzyl)imino]methyl‐3,7‐dihydro‐4 H ‐pyrrolo[2,3‐ d ]pyrimidine‐4‐one 7b‐e derivatives as potential tyrosine kinase inhibitors. These compounds were synthesized by condensation reaction using 2‐tritylamino‐4‐oxo‐4,7‐dihydro‐3 H ‐pyrrolo[2,3‐ d ]pyrimidine‐5‐carbaldehyde 5 and appropriate benzylamines followed by detritylation. Compounds were evaluated for their inhibitory activity toward tyrosine phosphorylation for the pp60 c‐Src tyrosine kinase. Compounds 7a, 7d , and 7e demonstrated potent inhibitory activities against pp60 c‐Src tyrosine kinase with IC 50 values of 13.9, 34.5, and 78.4 μM, respectively. Dihalogenated compounds 7d and 7e have 3 to 7‐times lower IC 50 values than that of the parent compound 7a .