Alpha,alpha-difluoro-beta-ketophosphonates as potent inhibitors of protein tyrosine phosphatase 1B.
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.
Li
Xianfeng
X
Affymax, Inc., 4001 Miranda Avenue, Palo Alto, CA 94304, USA. xli@galieopharma.com
Bhandari
Ashok
A
Holmes
Christopher P
CP
Szardenings
Anna K
AK
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D017027:Protein Tyrosine Phosphatases