The Hedgehog(Hh)signaling pathway was highly conserved in human and involved in body patterns and organ development during embryo development,but it was quiescent in adults except for tissue maintenance and repair.With regard to Hh signaling pathway,the 12 transmembrane receptor PTCH was a negative regulator of the seven transmembrane receptor SMO.PTCH was the receptor for the Hh ligand and inhibits SMO without the ligand.Abnormal activation of Hedgehog signaling pathway was linked to several human solid tumors,such as basal cell carcinomas,medulloblastoma,prostate cancer,chronic myelogenous leukemia [1].Hh signaling pathway has been a target for drug discovery.GDC-0449 [2] is the first arketed and targeted SMO Hh signaling pathway small molecular inhibitor,some other inhibitors are in clinical development.LDE225 [3] is the one inhibitor that is in phase III.Systematic study of SAR of GDC-0449 and LDE225 we devised analogue 1(Fig.1).The general synthetic rout used to prepare these compounds was illustrated in Scheme 1 and the potential inhibited Hh signaling pathway was measured by Gli mRNA.