We proceeded to synthesize a small panel of candidate Degraders based on this exit vector strategy, using 5 as a key intermediate. Routine cyclization chemistry, involving the ester-acid lithium salt 11, led to the important precursor 12, which underwent amide couplings with a small range of amine-linker-E3 ligase analogues to afford candidate degraders 13 -16 (Scheme 2). Affinities of the degraders to both BRD4 and CBP were again assessed biochemically using a FRET assay (Table ). Good balances of affinity were observed for degraders 13, 14, and 16, albeit with a marked increase in CBP IC50 values, whereas compound 15 was less active towards both bromodomains. Given the significant reduction in CBP affinities observed with our initial set of candidate Degraders, we next explored the piperazine exit vector, aiming to obtain Degrader molecules with more potent binary affinities to both targets. As before, a small panel of analogues was first synthesized to validate this position as a suitable exit vector and, in this instance, the ISOX-DUAL dimethylamino side chain was in such a clear drop in CBP binary affinity, given strong validation of the exit vector at this position (Table ). We decided to further test some of the candidate Degraders to assess whether, despite the unbalanced potency, they might be able to induce productive ternary complex formation.