title: Synthesis and mode of action of (125)I- and (3)H-labeled thieno[2,3-c]pyridine antagonists of cell adhesion molecule expression.
abstract: A series of thieno[2,3-c]pyridine antagonists of cell adhesion molecule (CAM) expression, such as A-205804 (1) and A-249377 (2), selectively suppressed the induced expression of E-selectin and ICAM-1 over VCAM-1. In an effort to explore the biological mechanism of action of these inhibitors, we synthesized (125)I- and (3)H-labeled thieno[2,3-c]pyridines 5 and 6. An isolated diazonium tetrafluoroborate salt efficiently trapped Na(125)I on very small scale (7.5 microg of Na(125)I), providing the corresponding (125)I-labeled thieno[2,3-c]pyridine in modest yield. Preliminary mechanistic investigations using these radiolabeled compounds revealed that, upon incubation with human umbilical vein endothelial cells (HUVECs), these inhibitors of CAM expression translocated to the cell nucleus and were noncovalently associated with macromolecules of molecular weight greater than 650 kDa.
authors.affiliation: Abbott Laboratories, Metabolic Diseases Research, Pharmaceutical Products Division, Department 04MJ, Building AP10, 100 Abbott Park Road, Abbott Park, Illinois 60064-3500, USA. gui-dong.zhu@abbott.com
authors.forename: Gui-Dong
authors.initials: GD
authors.lastname: Zhu
authors.forename: Verlyn
authors.initials: V
authors.lastname: Schaefer
authors.forename: Steven A
authors.initials: SA
authors.lastname: Boyd
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Okasinski
mesh_terms: D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D002850:Chromatography, Gel; D006801:Humans; D007457:Iodine Radioisotopes; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014316:Tritium
chemical_list: D015815:Cell Adhesion Molecules; D007457:Iodine Radioisotopes; D011725:Pyridines; D014316:Tritium