956895-37-7Relevant academic research and scientific papers
Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease
-
, (2016/11/21)
A method of treating a glomerular disease selected from the group consisting of mesangial proliferative glomerulonephritis, collapsing glomerulopathy, proliferative lupus nephritis, crescentic glomerulonephritis and membranous nephropathy in a subject com
Synthesis and Evaluation of Hybrid Structures Composed of Two Glucosylceramide Synthase Inhibitors
Vandenberg, Richard J.B.H.N.,Vanrijssel, Erwin R.,Ferraz, Maria Joao,Houben, Judith,Strijland, Anneke,Donker-Koopman, Wilma E.,Wennekes, Tom,Bonger, Kimberly M.,Ghisaidoobe, Amar B. T.,Hoogendoorn, Sascha,Vandermarel, Gijsbert A.,Codée, Jeroen D. C.,Overkleeft, Herman S.,Aerts, Johannes M. F. G.
, p. 2042 - 2062 (2015/12/23)
Glucosylceramide metabolism and the enzymes involved have attracted significant interest in medicinal chemistry, because aberrations in the levels of glycolipids that are derived from glucosylceramide are causative in a range of human diseases including lysosomal storage disorders, type2 diabetes, and neurodegenerative diseases. Selective modulation of one of the glycoprocessing enzymes involved in glucosylceramide metabolism - glucosylceramide synthase (GCS), acid glucosylceramidase (GBA1), or neutral glucosylceramidase (GBA2) - is therefore an attractive research objective. In this study we took two established GCS inhibitors, one based on deoxynojirimycin and the other a ceramide analogue, and merged characteristic features to obtain hybrid compounds. The resulting 39-compound library does not contain new GCS inhibitors; however, a potent (200nm) GBA1 inhibitor was identified that has little activity toward GBA2 and might therefore serve as a lead for further biomedical development as a selective GBA1 modulator. Taking the best of both: Two established glucosylceramide synthase (GCS) inhibitors were merged via convergent synthesis to obtain hybrid compounds. Members of this 39-compound library have characteristics of both parent GCS inhibitors. No new GCS inhibitors were established, but a potent (200nm) acid glucosylceramidase (GBA1) inhibitor was identified. This adamantanemethyloxypenanoic acid pyrrolidene-substituted derivative of eliglustat can serve as a lead for further biomedical development of selective GBA1 modulators.
2-ACYLAMINOPROPOANOL-TYPE GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
-
Page/Page column 94; 95, (2010/04/27)
A compound for use in treating polycystic kidney disease is represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of treating polycystic kidney disease in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. Methods of treating in polycystic kidney disease in a subject in need thereof respectively comprise administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof
2-ACYLAMINOPROPOANOL-TYPE GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
-
Page/Page column 112, (2009/01/24)
A compound is represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of treating
