Synthesis of thioridazine-VLA-4 antagonist hybrids using N-propargyl northioridazine enantiomers

Abstract

Herein, we report the synthesis of thioridazine-VLA-4 hybrid epimers. These hybrid molecules were obtained by means of a click reaction involving N-propargyl northioridazine enantiomers and an azide containing VLA-4 antagonist. A synthesis of northioridazine enantiomers from racemic thioridazine was developed and the absolute stereochemistry was confirmed by X-ray crystallography. Access to N-substituted thioridazine analogs may reveal that this phenothiazine core has therapeutic potential in other disease avenues.

Graphical Abstract

Keywords:

• Click
• northioridazine
• thioridazine
• VLA-4

Acknowledgments

We would like to thank the Arrow Bone Marrow Transplant Foundation for their financial support with an Arrow HCC PhD Scholarship.

Disclosure statement

There are no conflicts of interest to declare.

Additional information

Funding

This study was supported by the Arrow Bone Marrow Transplant Foundation for their financial support with an Arrow HCC PhD Scholarship.