Synthesis and Hypoglycemic Activity
of Aryl(Hetaryl)Propenoic Cyanopyrrolidine Amides1
S. O. Kuranova, 1, M. E. Blokhina, b, S. A. Borisova, M. V. Khvostova, b,
O. A. Luzinaa, and N. F. Salakhutdinova, b
aVorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
Novosibirsk, 630090 Russia
bNovosibirsk State University, Novosibirsk, 630090 Russia
1Abbreviations: GTT, glucose tolerance test; DPP-4, dipeptidyl peptidase-4; DM-2, type 2 diabetes mellitus; GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulinotropic polypeptide.
1Corresponding author: fax: (383) 330 9752; e-mail: s.o.kuranov@chemomsu.ru.
Received 22 February, 2019
Abstract—A series of amides based on (2S)-cyanopyrrolidine and α, β-unsaturated aryl- and hetarylcarboxylic acids have been synthesized. The dependence of the hypoglycemic activity of compounds on the structure of the aromatic fragment has been studied in the oral glucose tolerance test in mice. Amides based on (E)-3-phenylprop-2-enoic and (E)-3-(4-methoxyphenyl)prop-2-enoic acids and (2S)-cyanopyrrolidine have been shown to significantly reduce blood glucose levels in mice. The observed hypoglycemic effect at a dose of 10 mg/kg is comparable to the effect of hypoglycemic drug vildagliptin.
Keywords: diabetes mellitus type 2, cyanopyrrolidine, oral glucose tolerance test, hypoglycemic activity
DOI: 10.1134/S1068162019050078