title: Discovery and structural optimization of pyrazole derivatives as novel inhibitors of Cdc25B.
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.
authors.affiliation: The National Center for Drugs Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D013876:Thiophenes; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases