Design and synthesis of macrocyclic inhibitors of phosphatase cdc25B

Stefan Bäurle; Thorsten Blume; Judith Günther; Daniela Henschel; Roman C Hillig; Manfred Husemann; Anne Mengel; Christian Parchmann; Elke Schmid; Werner Skuballa

doi:10.1016/j.bmcl.2004.01.052

Design and synthesis of macrocyclic inhibitors of phosphatase cdc25B

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1673-7. doi: 10.1016/j.bmcl.2004.01.052.

Authors

Stefan Bäurle¹, Thorsten Blume, Judith Günther, Daniela Henschel, Roman C Hillig, Manfred Husemann, Anne Mengel, Christian Parchmann, Elke Schmid, Werner Skuballa

Affiliation

¹ Schering AG, Research Center Europe, D-13342 Berlin, Germany. stefan.baeurle@schering.de

PMID: 15026048
DOI: 10.1016/j.bmcl.2004.01.052

Abstract

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.

MeSH terms

Cell Cycle Proteins / antagonists & inhibitors*
Cell Cycle Proteins / metabolism
Drug Design*
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / metabolism
Structure-Activity Relationship
cdc25 Phosphatases / antagonists & inhibitors*
cdc25 Phosphatases / metabolism

Substances

Cell Cycle Proteins
Protease Inhibitors
cdc25 Phosphatases