Synthesis and evaluation of anilinohexafluoroisopropanols as activators/modulators of LXRalpha and beta.

Article Details

Citation
Copy to clipboard

Panday N, Benz J, Blum-Kaelin D, Bourgeaux V, Dehmlow H, Hartman P, Kuhn B, Ratni H, Warot X, Wright MB

Synthesis and evaluation of anilinohexafluoroisopropanols as activators/modulators of LXRalpha and beta.

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5231-7. Epub 2006 Jul 31.

PubMed ID
16876993 [ View in PubMed
]
Abstract

A series of branched and unbranched anilinohexafluoroisopropanols related to the known sulfonamide T0901317 were prepared and evaluated as activators/modulators of both LXRalpha and LXRbeta. A structure-activity relationship was established and compounds with high potency on both the receptors were identified. Many compounds showed a tendency toward selectivity for LXRbeta versus LXRalpha. Several analogues were evaluated for effects on plasma lipoprotein levels in mice. A few of these significantly raised HDL-cholesterol levels in plasma but showed markedly different effects on liver triglyceride content, suggesting that this series may yield candidates with improved efficacy/safety profiles compared to existing molecules.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TO-901317Oxysterols receptor LXR-alphaIC 50 (nM)30N/AN/ADetails
TO-901317Oxysterols receptor LXR-alphaEC 50 (nM)250N/AN/ADetails