Synthesis and Profiling of a Diverse Collection of Azetidine-Based Scaffolds for the Development of CNS-Focused Lead-like Libraries

The synthesis and diversification of a densely functionalized
azetidine
ring system to gain access to a wide variety of fused, bridged, and
spirocyclic ring systems is described. The in vitro physicochemical
and pharmacokinetic properties of representative library members are
measured in order to evaluate the use of these scaffolds for the generation
of lead-like molecules to be used in targeting the central nervous
system. The solid-phase synthesis of a 1976-membered library of spirocyclic
azetidines is also described.