Discovery of tetrahydro-cyclopenta[b]indole as selective LXRs modulator

A series of tetrahydro-cyclopenta[b]indoles modulating the activity of the liver-X-receptor (LXR) were derived from a high throughput screening hit. The potency and selectivity for LXRβ versus LXRα was improved. One compound, administered to wild-type mice modestly increased plasma HDL-cholesterol with no change in plasma triglycerides (TG) and reduced effects on liver TG content compared to T0901317. This novel series of LXR agonists shows promise to improve therapeutic efficacy with reduced potential to increase TG.

Graphical abstractA novel series of selective LXRs modulator derived from a high throughput screening hit is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide