Synthesis and mode of action of (125)I- and (3)H-labeled thieno[2,3-c]pyridine antagonists of cell adhesion molecule expression.
J Org Chem
; 67(3): 943-8, 2002 Feb 08.
Article
in En
| MEDLINE
| ID: mdl-11856042
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridines
/
Cell Adhesion Molecules
Limits:
Humans
Language:
En
Journal:
J Org Chem
Year:
2002
Document type:
Article
Affiliation country: