OBJECTIVETo synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro.

METHODSEleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl bromide with substituted phenyl piperazine pyridazinones.

RESULTSThe 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.

CONCLUSIONThe 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.

Diabetes Mellitus, Type 2 ; drug therapy ; Dipeptidyl-Peptidase IV Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; Pyrrolidines ; chemistry

OBJEVTIVETo synthesize phenoxybutyric acid derivatives as 5α-reductase inhibitors and test their biological activities in vitro.

METHODSEight analogues as nonsteroidal 5α-reductase inhibitors were designed and synthesized by substitution reaction of 6-(4-phenyl-piperazine-1-yl)-3(2H)-pyridazinone with phenoxybutyric acid derivatives.

RESULTS AND CONCLUSIONThe structures of the compounds were characterized by 1H-NMR and MS. Biological evaluation indicated that 7 out of the 8 compounds exhibited moderate 5α-reductase inhibitory activities, especially the compounds A1 and A7 with inhibition rates reaching 12.50% and 19.64% at the concentration of 3.3 × 10⁻⁵ mol/L, respectively.

5-alpha Reductase Inhibitors ; chemical synthesis ; pharmacology ; Butyrates ; chemistry ; pharmacology ; Drug Design