Synthesis of BMS-309403-related compounds, including [¹⁴C]BMS-309403, a radioligand for adipocyte fatty acid binding protein.
Adipocyte fatty acid binding protein (A-FABP; FABP4), which is predominantly expressed in macrophages and adipose tissue, regulates fatty acid storage and lipolysis, and is also an important mediator of inflammation. Here, we report a synthesis of (14)C-labeled 2-[2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy]acetic acid (BMS309403), a potent and selective small-molecular FABP4 inhibitor, as a chemical tool for investigating the roles of FABP4 in inflammatory and metabolic disorders. The structure-activity relationship of several BMS derivatives for inhibition of FABP4 is also reported.
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
Toshihiko
T
Okada
Makoto
M
Hiromura
Masato
M
Otsuka
Shuichi
S
Enomoto
Hiroyuki
H
Miyachi
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002250:Carbon Radioisotopes / Q000737:chemistry; D003198:Computer Simulation; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
C559288:2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D002250:Carbon Radioisotopes; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D011720:Pyrazoles