Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP)

Richard Sulsky; David R Magnin; Yanting Huang; Ligaya Simpkins; Prakash Taunk; Manorama Patel; Yeheng Zhu; Terry R Stouch; Donna Bassolino-Klimas; Rex Parker; Thomas Harrity; Robert Stoffel; David S Taylor; Thomas B Lavoie; Kevin Kish; Bruce L Jacobson; Steven Sheriff; Leonard P Adam; William R Ewing; Jeffrey A Robl

doi:10.1016/j.bmcl.2006.12.044

Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP)

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3511-5. doi: 10.1016/j.bmcl.2006.12.044. Epub 2006 Dec 21.

Affiliation

¹ Department of Metabolic Disease Chemistry, Bristol Myers-Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. [email protected]

PMID: 17502136
DOI: 10.1016/j.bmcl.2006.12.044

Abstract

Herein we report the first disclosure of biphenyl azoles that are nanomolar binders of adipocyte fatty acid binding protein (aFABP or aP2) with up to thousand-fold selectivity against muscle fatty acid binding protein and epidermal fatty acid binding protein. In addition a new radio-ligand to determine binding against the three fatty acid binding proteins was also synthesized.

MeSH terms

Adipocytes / drug effects*
Adipocytes / metabolism
Animals
Azoles / antagonists & inhibitors*
Binding Sites
Biphenyl Compounds / antagonists & inhibitors*
Disease Models, Animal
Epidermis / metabolism
Fatty Acid-Binding Proteins / antagonists & inhibitors*
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / pharmacology*
Hypolipidemic Agents / chemical synthesis
Hypolipidemic Agents / pharmacology*
Mice
Models, Chemical
Radioligand Assay

Substances

Azoles
Biphenyl Compounds
Fatty Acid-Binding Proteins
Hypoglycemic Agents
Hypolipidemic Agents
diphenyl