| Abstract [eng] |
It is known that 1,4-diazepine heterocycles fused with nitrogen-based heterocycles exhibit diverse biological properties such as antimalarial [1], antitumor [2] and antiviral [3] activity. For example, a 1,6,7,8- tetrahydropyrazolo[3,4-b][1,4]diazepine derivative inhibits growth of P. falciparum and has potential for treating malaria [1], whereas 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepine derivative inhibits the growth of the cell line IGROV1 responsible for ovarian cancer [2]. Another example includes 5,6,7,8-tetrahydro-4H-pyrazolo[1,5- a][1,4]diazepine-2-carboxamide derivative which inhibits the respiratory syncytial virus (RSV) polymerase complex [3]. In this work, we synthesized novel pyrazole and indole-fused tetrahydro-1,4-diazepinones. For the optimization of the reaction conditions, reactivity of 1H-pyrazole-5(3)-carboxylates towards alkylation with epichlorohydrin was investigated. Obtained 1-(oxiran-2-ylmethyl)-1H-pyrazole-5-carboxylates were further treated with ammonia resulting in oxirane ring-opening and subsequent cyclisation affording tetrahydro-4Hpyrazolo[ 1,5-a][1,4]diazepin-4-ones. The obtained cyclization products were further functionalized by treatment with N-chloro-, bromo- and iodosuccinimides to obtain 2(3)-halogenated tetrahydro-4H-pyrazolo[1,5- a][1,4]diazepin-4-ones. An analogous two-step synthesis approach was further used to expand the study and to obtain tetrahydro[1,4]diazepino[1,2-a]indol-1-one derivatives from corresponding indole-2-carboxylates [4]. The structures of novel heterocyclic compounds were confirmed by 1H, 13C, and 15N-NMR spectroscopy. |
