Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP).
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.
Sulsky
Richard
R
Department of Metabolic Disease Chemistry, Bristol Myers-Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. sulskyr@bms.com
Magnin
David R
DR
Huang
Yanting
Y
Simpkins
Ligaya
L
Taunk
Prakash
P
Patel
Manorama
M
Zhu
Yeheng
Y
Stouch
Terry R
TR
Bassolino-Klimas
Donna
D
Parker
Rex
R
Harrity
Thomas
T
Stoffel
Robert
R
Taylor
David S
DS
Lavoie
Thomas B
TB
Kish
Kevin
K
Jacobson
Bruce L
BL
Sheriff
Steven
S
Adam
Leonard P
LP
Ewing
William R
WR
Robl
Jeffrey A
JA
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001393:Azoles / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008956:Models, Chemical; D011869:Radioligand Assay
D001393:Azoles; D001713:Biphenyl Compounds; D050556:Fatty Acid-Binding Proteins; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; C010574:biphenyl