SMALL MOLECULE INHIBITORS OF PI3-KINASE SIGNALING

摘要

Provided are certain 1,2,3-triazole and 1,2,3-triazole dimer analogs of DM-PIT-1 which are second-generation selective non-phosphoinositide small molecule inhibitors of phosphatidylinositol-3,4,5-trisphosphate (PIP3), including 1,2,3-triazoles represented by formula (I) where: Ar represents aryl or heteroaryl; X represents O or S; each of Ra, Rb, Rc, and Rd independently represents hydrogen, halogen, C1-C10alkyl, -OH, -CF3, aryl, amino, or nitro; and Ar is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-Cioalkyl, -OH, -CF3, amino, and nitro. Also provided are pharmaceutical compositions comprising compounds of the invention and a pharmaceutical carrier. Also provided are methods of inhibiting PIP3-mediated signaling in a cell and treating cancer using compounds of the invention.