Discovery of tetrahydro-cyclopenta[b]indole as selective LXRs modulator
Hassen Ratni1, Denise Blum-Kaelin, Henrietta Dehmlow
1F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Preclinical Research, CH-4070 Basel, Switzerland.
Abstract:
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 LXRbeta versus LXRalpha 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.
More Related Videos
10:17Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
06:34Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
Related Concept Videos
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Woodward–Hoffmann Selection Rules and Microscopic Reversibility
Cycloaddition Reactions: MO Requirements for Thermal Activation
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Photochemical Electrocyclic Reactions: Stereochemistry
Selection Rules: Photochemical Activation
