Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors

The SAR of a series of small molecule Bcl-2 inhibitors is reported. Anti-apoptotic Bcl-2 protects cells from apoptosis by binding to pro-apoptotic members of the Bcl-2 family thereby playing a role in tumour survival in response to chemo- or radiation therapy. We describe a series of phenyl pyrazoles that have high affinity for Bcl-2 and rationalise the observed SAR by means of an X-ray crystal structure.