| Autor: |
Morkovnik, A., Spasov, A., Kuz'menko, T., Kucheryavenko, A., Divaeva, L., Koshchienko, Yu., Anisimova, V., Kuzmina, L., Rogova, N., Kuznetsova, V., Chepljaeva, N., Solovyova, O., Taran, A., Vorobiev, E., Aleshin, D., Sirotenko, V., Gajdukova, K., Bogoslavtseva, M. |
| Předmět: |
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| Zdroj: |
Russian Chemical Bulletin; Nov2015, Vol. 64 Issue 11, p2622-2631, 10p |
| Abstrakt: |
Based on the X-ray crystallography and H NMR spectroscopy data and quantum chemical studies, it was found that 1(11) H-2, 3, 4, 5-tetrahydro[1, 3]diazepino[1, 2- a]benzimidazole (1) exists almost exclusively in the 1 H-prototropic form. To prepare the fixed 11 H-diazepinobenzimidazole forms of 1, 1-R-2-(4-chlorobutylamino)benzimidazoles (R = Me, N=CHAr) were synthesized, which underwent thermal cyclization with the formation of a mixture of 11-Rsubstituted diazepine 1 and 1-R-2-(pyrrolidin-1-yl)benzimidazole. Alkylation of diazepine 1 in a neutral medium regioselectively gave 11-R-diazepinobenzimidazoles in high yield. Their 1-substituted isomers were obtained by carrying out this reaction in the system NaH-THF. The N(11)-derivatives of diazepinobenzimidazole 1 were found to inhibit dipeptidyl peptidase 4 (DPP-4), but less actively than a comparator drug sitagliptin. The compounds under study did not exhibit antiglycation action in vitro and virtually did not affect activity of α-glucosidase and glycogen phosphorylase. However, they are characterized by a strong antiaggregant effect, making these derivatives promising for further studies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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