The design, synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid.


The plant natural product, valerenic acid (1, I) was chosen as a desirable scaffold for the generation of a novel screening library due to its drug-like physicochem. parameters (such as Log P, hydrogen bond donor/acceptor counts, and mol. wt.). An 11-membered amide library was subsequently generated using parallel soln.-phase synthesis and Ghosez’s reagent. The chem. structures of all semi-synthetic analogs were elucidated following anal. of the NMR, MS, UV and IR data. The structures of compds. 8 and 11 (VIII and XI, resp.) were also confirmed by X-ray crystallog. anal. All library members were evaluated for their ability to inhibit the release of IL-8 and TNF-α. Six analogs showed moderate activity in the IL-8 assay with IC50 values of 2.8-8.3 μM, while none of the tested compds. showed any significant effect on inhibiting TNF-α release.

Bioorganic & Medicinal Chemistry Letters