Synthesis and mode of action of 125I- and 3H-labeled thieno[2,3-c]pyridine antagonists of cell adhesion molecule expression

被引：8
|
作者：
Zhu, GD [1 ]
Schaefer, V [1 ]
Boyd, SA [1 ]
Okasinski, GF [1 ]
机构：
[1] Abbott Labs, Metab Dis Res, Div Pharmaceut Prod, Abbott Pk, IL 60064 USA
来源：
JOURNAL OF ORGANIC CHEMISTRY | 2002年 / 67卷 / 03期
关键词：
D O I：
10.1021/jo016171j
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
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 I-125- and H-3-labeled thieno[2,3-c]pyridines 5 and 6. An isolated diazonium tetrafluoroborate salt efficiently trapped (NaI)-I-125 on very small scale (7.5 mug of (NaI)-I-125), providing the corresponding I-125-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.
引用
收藏
页码：943 / 948
页数：6
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