Design, synthesis and characterization of cyanopyrrolidine-bearing compounds as DPP-4 inhibitors / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro.</p><p><b>METHODS</b>Eleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl bromide with substituted phenyl piperazine pyridazinones.</p><p><b>RESULTS</b>The structures of the compounds were characterized by (1)H-NMR and MS spectra. Biological evaluation indicated that most of the compounds exhibited moderate inhibitory activities against DPP4.</p><p><b>CONCLUSION</b>The preliminary bioassay indicates that all the synthesized compounds have moderate DPP-4 inhibition activity, especially the compounds 1j and 1k with inhibition rates reaching 26.14% and 34.15% at the concentration of 1×10(5) nmol/L, respectively.</p>