N-(5-(BIPHEN-4-YLMETHYLOXY)PENTYL)-SUBSTITUTED IMINOSUGARS AS INHIBITORS OF GLUCOSYLCERAMIDE SYNTHASE

• Main Authors: VAN BOECKEL, Stan, AERTS, Johannes Maria Franciscus Gerardus, VAN DEN BERG, Richard, GHISAIDOOBE, Amar, OVERKLEEFT, Herman Steven
• Format: Patent
• Language: English; French; German
• Published: 13.10.2021
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention concerns D-deoxygalactonojirimycin derivatives shown below. These compounds display an increased inhibitory potency towards GCS, and/or an increased inhibitory potency towards GBA2, and/or a decreased inhibitory potency towards GBA1, relative to known deoxynojirimycin derivatives of the same D -galacto configuration. Therefore, compounds of the present invention are effective in the treatment of diseases which are associated with an irregular level of cytosolic or lysosomal glucosylceramide and/or higher glycosphingolipids, such as a lysosomal storage disorder, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis, Sialidosis, Niemann Pick disease type C and AMRF, or a symptom of one of the diseases collectively classed as metabolic syndrome, such as obesity, insulin resistance, hyperlipidemia, hypercholesterolemia, polycystic kidney disease, type II diabetes and chronic inflammation, or a neurodenegerative disorder, such as Parkinson disease or Lewy-body dementia.