Dimeric small molecule potentiators of apoptosis

A pro-apoptotic Smac (second mitochondria-derived activator of caspases) peptide mimetic dimeric compound of the general formula M1-L-M2, wherein moieties M1 and M2 are monomeric Smac mimetics and L is a linker covalently linking M1 and M2 in the active dimeric compound, wherein M1-L-M2 is of formula II,

• wherein:
• R1 and R1′ are selected from hydrogen, optionally substituted methyl, and hydroxyl;
• R2 and R2′ are selected from optionally substituted methyl and optionally substituted ethyl;
• R3 and R3′ are selected from CH2, NH, O and S;
• R4 and R4′ are selected from CH and N;
• R5-R8, and R5′-R8′ are selected from hydrogen, optionally hetero-, optionally substituted alkyl, optionally hetero-, optionally substituted alkenyl, optionally hetero-, optionally substituted alkynyl, optionally hetero-, optionally substituted aryl, wherein optionally either R6 and R7 as well as R6′ and R7′ or R7 and R8 as well as R7′ and R8′ are connected in 5- to 8-membered rings;
• and
• L is a contiguous chain of between 2 and 200 atoms, having a MW between 20 D and 2 KD that can incorporate substitution, heteroatoms, unsaturation and cyclic aromatic and heteroaromatic portions,
• or a pharmaceutically-acceptable salt thereof.