A　series　of　novel　hedgehog　signaling　pathway　inhibitors　have　been　designed　by　structural　modification　based　on　the　former　reported　scaffold　of　4-(2-pyrimidinylamino)benzamide.　The　SAR　for　this　series　was　described　and　many　derivatives　showed　potent　inhibitory　activity.　Among　these　compounds,　compounds　12af　and　12bf　were　identified　to　have　high　potency　and　optimal　PK　profiles.　Although　both　of　compounds　12af　and　12bf　did　not　show　strong　antitumor　efficacy　in　LS-174T　nude　mice　model,　they　were　promising　candidates　as　Hh　signaling　inhibitors　due　to　great　potency　against　Hh　signaling　pathway　and　outstanding　PK　properties,　deserving　further　evaluation　in　other　Hh　signaling　operative　tumor　models.　(C)　2016　Elsevier　Masson　SAS.　All　rights　reserved.