Patent Evaluation: Novel inhibitors of atherosclerotic intimal thickening

Summary

Novelty: Novel inhibitors of atherosclerotic intimal thickening which contain pyridine derivatives are disclosed. These agents have strong inhibitory effects against HMG-CoA reductase, against proliferation of aortic intimal smooth muscle cells, migration of aortic medial smooth muscle cells and adhesion of blood cells to endothelial cells.

Biology: Inhibitory effects on migration of aortic smooth muscle cells were determined in vitro using aortic slices from male Sprague Dawley rats. The specified compound demonstrated 100% inhibition of PDGF and SMC-CM at 10^-5M. The inhibitory effects on the proliferation of aortic intimal and medial smooth muscle cells was also demonstrated. The specified compound demonstrated 100% inhibition at 10^-5 and 10^-6M. Inhibitory effects on [³H]-thymidine uptake adhesion of leukaemic cells and adhesion of J774 macrophages are also reported.

Chemistry: Three compounds are specifically claimed including 3,5-dihydroxy-7-[6′-cyclopropyl-3′-ethyl-4′-(4″-fluorophenyl)-2′-methylthieno[2,3-b]pyridin-5′-yl]hept-6-enoic acid.