Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

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Zuercher WJ, Buckholz RG, Campobasso N, Collins JL, Galardi CM, Gampe RT, Hyatt SM, Merrihew SL, Moore JT, Oplinger JA, Reid PR, Spearing PK, Stanley TB, Stewart EL, Willson TM

Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

J Med Chem. 2010 Apr 22;53(8):3412-6. doi: 10.1021/jm901797p.

PubMed ID
20345102 [ View in PubMed
]
Abstract

Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TO-901317Oxysterols receptor LXR-alphaEC 50 (nM)63.1N/AN/ADetails