Experimental and Computational Investigation of the Oxime Bond Stereochemistry in c-Jun N-terminal Kinase 3 Inhibitors 11<i>H</i>-Indeno[1,2-<i>b</i>]quinoxalin-11-one Oxime and Tryptanthrin-6-oxime
Vladislava V. Matveevskaya,
Dmitry I. Pavlov,
Anastasia R. Kovrizhina,
Taisiya S. Sukhikh,
Evgeniy H. Sadykov,
Pavel V. Dorovatovskii,
Vladimir A. Lazarenko,
Andrei I. Khlebnikov,
Andrei S. Potapov
Affiliations
Vladislava V. Matveevskaya
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia
Dmitry I. Pavlov
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia
Anastasia R. Kovrizhina
Kizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin Ave., 634050 Tomsk, Russia
Taisiya S. Sukhikh
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia
Evgeniy H. Sadykov
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia
Pavel V. Dorovatovskii
National Research Centre “Kurchatov Institute”, Kurchatov Square 1, 123182 Moscow, Russia
Vladimir A. Lazarenko
National Research Centre “Kurchatov Institute”, Kurchatov Square 1, 123182 Moscow, Russia
Andrei I. Khlebnikov
Kizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin Ave., 634050 Tomsk, Russia
Andrei S. Potapov
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia
11H-Indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) and tryptanthrin-6-oxime are potent c-Jun N-terminal kinase 3 (JNK-3) inhibitors demonstrating neuroprotective, anti-inflammatory and anti-arthritic activity. However, the stereochemical configuration of the oxime carbon–nitrogen double bond (E- or Z-) in these compounds was so far unknown. In this contribution, we report the results of the determination of the double bond configuration in the solid state by single crystal X-ray diffraction and in solution by 1D and 2D NMR techniques and DFT calculations. It was found that both in the solid state and in solution, IQ-1 adopts the E-configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed Z-configuration that could be stabilized only by an intramolecular hydrogen bond.
