Design and synthesis of macrocyclic inhibitors of phosphatase cdc25B.
Based on molecular modeling studies, macrocyclic inhibitors of phosphatase cdc25B were synthetically derived from steroids. A preliminary SAR for this new template was elaborated. A series of compounds shows inhibition of cdc25B in the low micromolar range and good selectivity versus other phosphatases. The compounds did not show a significant antiproliferative effect in MaTu or HaCaT cells.
Bäurle
Stefan
S
Schering AG, Research Center Europe, D-13342 Berlin, Germany. stefan.baeurle@schering.de
Blume
Thorsten
T
Günther
Judith
J
Henschel
Daniela
D
Hillig
Roman C
RC
Husemann
Manfred
M
Mengel
Anne
A
Parchmann
Christian
C
Schmid
Elke
E
Skuballa
Werner
W
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018797:Cell Cycle Proteins; D011480:Protease Inhibitors; D020687:cdc25 Phosphatases