Tetrahydrofuran as a Scaffold for Peptidomimetics. Application to the Design and Synthesis of Conformationally Constrained Metalloproteinase Inhibitors

Enantiopure functionalized tetrahydrofurans were synthesized as prototypical conformationally constrained analogs of acyclic succinic acid-based inhibitors of metalloproteinases. While preliminary docking study showed good congruence with a potent inhibitor, the biological results were disappointing. Molecular dynamics simulation revealed the weakness of the H-bond interactions.