In　present　study,　a　series　of　novel　containing　trifluoromethyl　4-(2-pyrimidinylamino)　benzamide　derivatives　were　designed　by　the　fluorine　scan　strategy.　Their　Hh　signaling　inhibitory　activities　were　evaluated　by　Gli-luciferase　reporter　method.　The　comprehensive　SAR　was　discussed　and　several　derivatives　were　found　to　display　more　potent　Hh　signaling　inhibitory　activity　than　positive　drug　vismodegib.　Compound　13d　was　the　most　potent　compound　with　IC50　of　1.44　nM　against　Hh　signaling　pathway　and　also　exhibited　optimal　PK　properties　in　the　in　vivo　PK　properties　study,　deserved　as　an　ideal　lead　compound　for　further　study　in　future.　(C)　2016　Elsevier　Ltd.　All　rights　reserved.