Synthesis of bioactive substituted morpholine compounds

摘要

Substituted morpholines are an important class of structures which have been found applications in diverse fields, particularly in medicinal chemistry research. Therefore, the importance of morpholine motif has attracted great interest in oriented synthesis, biological tests and pharmaceutical industries. In this research project, the applications of compounds containing morpholines in natural products and medicinal chemistry were reviewed. A novel, simple chemistry route of synthesizing cis-3,5disubstituted arylsulfonyl morpholine, including fused ring arylsulfonyl morpholine core compounds and alpha-hydroxyl amide arylsulfonyl morpholine compounds has been developed.;The developed chemistry can be applied to synthesis different substituted morpholine compounds, which provides a convenient pathway for the studies of structure-activity relationship (SAR) in drug development. Furthermore, the final compounds were tested in gamma-secretase assay. Most of the compounds have been found to be very active gamma-secretase inhibitors. Therefore, the compounds prepared in this work are potential candidates for the treatment of neurodegenerative disease such as Alzheimer's disease and Down syndrome or any other diseases caused by the deposition of Amyloid beta (Abeta).