Based on the hit compound 4 derived from focused library, a series of furo[2,3-d]pyrimidines were designed, synthesized and evaluated for the inhibitory activity against Akt1 kinase. And their structure-activity relationships were investigated. Of these compounds, 3a having 2-thienyl and methyl groups at R1 and R2 showed the most potent activity with an IC50 value of 24 μ M. Introduction of the thienyl groups at C-5 and C- 6 positions significantly improved potency compared to furyl and phenyl groups.