Novel hypoglycemic dihydropyridones serendipitously discovered from O- versus C-alkylation in the synthesis of VMAT2 antagonists.
Vesicular monoamine transporter type 2 (VMAT2) is a newly emerging target for both diagnostic and therapeutic applications in diabetes mellitus. In pursuit of novel VMAT2 antagonists, we identified a potent hypoglycemic agent with a novel dihydropyridone scaffold. Several analogs were designed and synthesized. A preliminary structure activity relationship (SAR) showed that the dihydropyridone scaffold is required for the activity.
Xie
Yuli
Y
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Raffo
Anthony
A
Ichise
Masanori
M
Deng
Shixian
S
Harris
Paul E
PE
Landry
Donald W
DW