Development of a new class of liver receptor homolog-1 (LRH-1) agonists by photoredox conjugate addition

• Published in: Bioorganic & medicinal chemistry letters Vol. 30; no. 16; p. 127293
• Main Authors: Cornelison, Jeffery L., Cato, Michael L., Johnson, Alyssa M., D'Agostino, Emma H., Melchers, Diana, Patel, Anamika B., Mays, Suzanne G., Houtman, René, Ortlund, Eric A., Jui, Nathan T.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.08.2020; Elsevier
• Subjects: Agonist; Aniline Compounds - chemical synthesis; Aniline Compounds - chemistry; Aniline Compounds - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Drug Development; Humans; Life Sciences & Biomedicine; LRH-1; Metabolic disease; Molecular Docking Simulation; Molecular Structure; Nuclear receptor; Oxidation-Reduction; Pharmacology & Pharmacy; Photochemical Processes; Photoredox; Physical Sciences; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - genetics; Science & Technology; Structure-Activity Relationship; Metabolic disease; Nuclear receptor; Agonist; LRH-1; Photoredox; INSERTION; QUATERNARY CARBONS; RADICALS

[Display omitted] LRH-1 is a nuclear receptor that regulates lipid metabolism and homeostasis, making it an attractive target for the treatment of diabetes and non-alcoholic fatty liver disease. Building on recent structural information about ligand binding from our labs, we have designed a series o...