Figure 3.

New molecules based on scaffold hopping from GSK650394 designed to interrogate several aspects of hinge binding interactions between CAMKK2 and the proposed inhibitors. Top row: Inhibitors retaining the topology of GSK650394 (5,6-fused ring systems with the cyclopentyl-substituted benzoic acid moiety attached to the 5-membered ring). Middle row: 5,6-fused systems with the cyclopentyl-substituted benzoic acid moiety appended to the 6-membered ring. Bottom row: Inhibitors with ring expansion (6,6-fused ring system) or ring deletion (single 6-membered ring as the hinge-binding core).