Acylpyrogallols as Inhibitors of Antiapoptotic Bcl-2 Proteins

A series of acylpyrogallols were designed, synthesized, and evaluated as small-molecule inhibitors of antiapoptotic Bcl-2 proteins. The most potent compound <b>9</b> (TM-179) binds to Bcl-2 with an IC<sub>50</sub> of 170 nM and to Mcl-1 with a <i>K</i><sub>i</sub> of 37 nM. Compound <b>9</b> potently inhibits cell growth and induces apoptosis in human breast and prostate cancer cell lines.