Based on a 3D-QSAR pharmacophore derived from a diverse set of known cyclin-dependent kinase 9(CDK9)inhibitors and a composite pharmacophore extracted from the complex structure of flavopiridol(FVP)-CDK9,thirty novel 5-fluoro-N2,N4-diphenylpyrimidine-2,4-diamine derivatives were designed and synthesized.Initial tests against four tumor cell lines with the sulforhodamine B(SRB)assay identified a series of potent compounds with GI50 values at a lower micromolar or submicromolar level.Most of the highly cytotoxic compounds exhibited potent inhibitory activities against both CDK2/cyclin E1 and CDK9/cyclin T1.Notably,inhibitions against the two enzymes were generally correlated well with the cytotoxicity of these compounds.Appreciable inhibition was also observed for selected compounds in the anti-HIV-1 assay.Docking studies on compounds 6d and 9g provided conducive clues to further structural optimization.