Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38.

Abstract

Several monoclonal antibodies and inhibitors targeting CD38, an ectoenzyme overexpressed on malignant plasma cells, have previously been discovered. Herein, we expand structure-activity relationships of reported small-molecule thiazoloquinolinones and show that several 4-cyclohexylamino analogues have potent binding affinity for CD38 using surface plasmon resonance. Moreover, active amine analogues could be acylated and functionalized with alkyne and fluorescein groups. Fluorescein analogue 21 bound selectively to CD38 overexpressing cells, demonstrating the potential utility of thiazoloquinolinones as small-molecule conjugates for the delivery of therapeutic and imaging agents.