Synthesis and biological activity of 4,5-polymethylenepyrazole-derived HMG-COA reductase inhibitors

New HMG-CoA reductase inhibitors, in which 3-substituted 4,5-polymethylenepyrazoles are employed as a hydrophobic anchor connected to tetrahydro-4-hydroxy-2H-pyran-2-one by a two-carbon bridge, were designed and synthesized to exhibit significant inhibitory activity comparable to mevinolin. The most potent enzyme inhibitor (11cc, IC₅₀=0.01 μM) is 4-fold more potent than lovastatin.