| Abstract
| - A series of thieno[2,3-c]pyridine antagonists of cell adhesion molecule (CAM) expression, such asA-205804 (1) and A-249377 (2), selectively suppressed the induced expression of E-selectin andICAM-1 over VCAM-1. In an effort to explore the biological mechanism of action of these inhibitors,we synthesized 125I- and 3H-labeled thieno[2,3-c]pyridines 5 and 6. An isolated diazoniumtetrafluoroborate salt efficiently trapped Na125I on very small scale (7.5 μg of Na125I), providingthe corresponding 125I-labeled thieno[2,3-c]pyridine in modest yield. Preliminary mechanisticinvestigations using these radiolabeled compounds revealed that, upon incubation with humanumbilical vein endothelial cells (HUVECs), these inhibitors of CAM expression translocated to thecell nucleus and were noncovalently associated with macromolecules of molecular weight greaterthan 650 kDa.
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