The first two cantharidin analogues displaying PP1 selectivity.
High pressure Diels-Alder reactions of furan and dimethylmaleate, and thiophene and maleimide resulted in two cantharidin analogues, 3 and 6 possessing PP1 selectivity (>40- and >30-fold selectivity) over PP2A. Both compounds exhibited moderate PP1 activity, 3 IC(50) 50 microM and 6 IC(50) 12.5 microM. Interestingly, the corresponding mono-ester derivatives of 3 showed no such selectivity.
McCluskey
Adam
A
Medicinal Chemistry Group, School of Biological and Chemical Sciences, The University of Newcastle, University Drive, Callaghan, Newcastle, NSW 2308, Australia. amcclusk@mail.newcastle.edu.au
Keane
Mirella A
MA
Walkom
Cecilia C
CC
Bowyer
Michael C
MC
Sim
Alistair T R
AT
Young
David J
DJ
Sakoff
Jennette A
JA
D002193:Cantharidin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D010749:Phosphoprotein Phosphatases; D002193:Cantharidin