Discovery and structural optimization of pyrazole derivatives as novel inhibitors of Cdc25B

Hai-Jun Chen; Yong Liu; Li-Na Wang; Qiang Shen; Jia Li; Fa-Jun Nan

doi:10.1016/j.bmcl.2010.03.040

Discovery and structural optimization of pyrazole derivatives as novel inhibitors of Cdc25B

Bioorg Med Chem Lett. 2010 May 1;20(9):2876-9. doi: 10.1016/j.bmcl.2010.03.040. Epub 2010 Mar 11.

Authors

Hai-Jun Chen¹, Yong Liu, Li-Na Wang, Qiang Shen, Jia Li, Fa-Jun Nan

Affiliation

¹ The National Center for Drugs Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

PMID: 20363629
DOI: 10.1016/j.bmcl.2010.03.040

Abstract

Structural optimization and preliminary structure-activity relationship studies of a series of N-substituted maleimide fused-pyrazole analogues with Cdc25B inhibitory activity, starting from a high-throughput screening hit, are illustrated. A simplified 3,5-diacyl pyrazole analogue was obtained as the most potent compound (118, IC(50)=0.12 microM) with a 270-fold increase in potency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Drug Discovery
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Humans
Kinetics
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / pharmacology
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology
cdc25 Phosphatases / antagonists & inhibitors*
cdc25 Phosphatases / metabolism

Substances

Antineoplastic Agents
Enzyme Inhibitors
Pyrazoles
Thiophenes
CDC25B protein, human
cdc25 Phosphatases