Alpha,alpha-difluoro-beta-ketophosphonates as potent inhibitors of protein tyrosine phosphatase 1B.
Bioorganic & medicinal chemistry letters 2004 Aug 16; 14(16):4301-6
Li X X, Bhandari A A, Holmes C CP, Szardenings A AK
Affymax, Inc., 4001 Miranda Avenue, Palo Alto, CA 94304, USA. xli@galieopharma.com
A novel series of inhibitors that contain an aryl alpha,alpha-difluoro-beta-ketophosphonate group has been synthesized and evaluated against protein tyrosine phosphatase 1B. These compounds exhibit strong inhibitory activity, the best of which has a K(i) value of 0.17 microM. These results demonstrate that aryl alpha,alpha-difluoro-beta-ketophosphonates are powerful phosphotyrosine mimetics for the development of potent PTP inhibitors.

