1,3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPARgamma partial agonists.

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Choi J, Park Y, Lee HS, Yang Y, Yoon S

1,3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPARgamma partial agonists.

Bioorg Med Chem. 2010 Dec 1;18(23):8315-23. doi: 10.1016/j.bmc.2010.09.068. Epub 2010 Oct 26.

PubMed ID
21030263 [ View in PubMed
]
Abstract

A new series of PPARgamma partial agonists, 1,3-diphenyl-1H-pyrazole derivatives, were identified using an improved virtual screening scheme combining ligand-centric and receptor-centric methods. An in vitro assay confirmed the nanomolar binding affinity of 1,3-diphenyl-1H-pyrazole derivatives such as SP3415. We also characterized the competitive antagonism of SP3415 against rosiglitazone at micromolar concentrations. They showed a PPARgamma partial agonistic activity similar to that of a known PPARgamma drug, pioglitazone, in a cell-based transactivation assay. Furthermore, the structure-activity relationships of the pyrazole derivatives were investigated through comparative molecular field analysis and binding mode analysis, which provided new insight concerning their partial agonistic effect on PPARgamma.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
3-FLUORO-N-[1-(4-FLUOROPHENYL)-3-(2-THIENYL)-1H-PYRAZOL-5-YL]BENZENESULFONAMIDEPeroxisome proliferator-activated receptor gammaIC 50 (nM)512N/AN/ADetails
PioglitazonePeroxisome proliferator-activated receptor gammaIC 50 (nM)855N/AN/ADetails
RosiglitazonePeroxisome proliferator-activated receptor gammaIC 50 (nM)199N/AN/ADetails