In　present　study,　a　novel　series　of　fluorine　containing　4-(2-pyrimidinylamino)　benzamide　analogues　were　designed　and　synthesized.　The　hedgehog　(Hh)　signaling　inhibitory　activities　for　these　compounds　were　evaluated　by　a　luciferase　reporter　method.　The　preliminary　SAR　was　discussed　and　many　compounds　showed　potent　Hh　signaling　inhibitory　activities.　Compound　15h　displayed　the　most　potent　inhibitory　activity,　with　an　IC50　of　0.050　nM.　This　paper　finds　the　introduction　of　fluorine　to　the　4-(2-pyrimidinylamino)　benzamide　scaffold　can　lead　to　a　novel　series　of　potent　Hh　signaling　pathway　inhibitors.　(C)　2017　Elsevier　Ltd.　All　rights　reserved.