Structure-guided design, synthesis and in vitro evaluation of a series of pyrazole-based fatty acid binding protein (FABP) 3 ligands

In order to create FABP3 ligands, a new series of pyrazole-based carboxylic acids were designed and synthesized based on the X-ray crystallographic result of the structure of BMS309403, other FABP subtype of FABP4–selective inhibitor–FABP4 complex as a template. We designed a series of pyrazole-based carboxylic acids as candidate ligands of heart fatty acid binding protein (H-FABP, or FABP3), based on a comparison of the X-ray crystallographic structures of adipocyte fatty acid binding protein (FABP4)–selective inhibitor (BMS309403) complex and FABP3–elaidic acid complex. Some of the synthesized compounds exhibited dual FABP3/4 ligand activity, and some exhibited selectivity for FABP3.