10.1016/S0014-827X(01)01077-1
The research focused on the development of a novel template, 5-acyloxy-5-hydroxymethyltetrahydro-2-furancarboxylate, for protein kinase C (PKC) binding. The purpose of this study was to synthesize and test a series of alkyl tetrahydrofuran-2-carboxylates as PKC ligands, which could potentially play a role in cellular signal transduction pathways and disease states. The researchers aimed to investigate whether these compounds could mimic a pharmacophore model comprising the C20–OH, C3–CO, and C9–OH groups, rather than the C13–CO moiety. The synthesis involved chemicals such as glycidyl 4-methoxyphenyl ether, lactol, 2-cyanotetrahydrofuran, and various esters, with the final compounds being 1–4. The study concluded that the new template did not offer significant advantages over previous models, and that finding a single isopharmacophoric group equivalent to phorbol’s C13–CO ester on simple conformationally constrained glycerol templates remains a challenge. The compounds showed binding affinities in the submicromolar range, similar to previous templates, indicating that the new template IV was not more effective than template I or II/III in terms of PKC binding affinity.
