Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2<i>H</i>)-one as Novel Scaffold for FABP4 Inhibition

Abstract

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.

Keywords

• fatty acid binding protein
• FABP4
• FABP4is
• FABP4 inhibitors
• pyridazinone
• computing assisted molecular design