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

Yoko Beniyama; Kenji Matsuno; Hiroyuki Miyachi

doi:10.1016/j.bmcl.2013.01.054

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

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1662-6. doi: 10.1016/j.bmcl.2013.01.054. Epub 2013 Jan 26.

Authors

Yoko Beniyama¹, Kenji Matsuno, Hiroyuki Miyachi

Affiliation

¹ Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 1-1-1, Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.

PMID: 23395658
DOI: 10.1016/j.bmcl.2013.01.054

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Biphenyl Compounds / chemistry
Crystallography, X-Ray
Drug Design*
Fatty Acid Binding Protein 3
Fatty Acid-Binding Proteins / chemistry*
Fatty Acid-Binding Proteins / metabolism
Humans
Kinetics
Ligands
Molecular Docking Simulation
Protein Binding
Protein Structure, Tertiary
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / metabolism

Substances

2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid
Biphenyl Compounds
FABP3 protein, human
FABP4 protein, human
Fatty Acid Binding Protein 3
Fatty Acid-Binding Proteins
Ligands
Pyrazoles
pyrazole