c-Jun氨基末端激酶3抑制剂11-茚并[1,2-]喹喔啉-11-酮肟和色胺酮-6-肟中肟键立体化学的实验与计算研究

Experimental and Computational Investigation of the Oxime Bond Stereochemistry in c-Jun N-terminal Kinase 3 Inhibitors 11-Indeno[1,2-]quinoxalin-11-one Oxime and Tryptanthrin-6-oxime.

作者信息

Matveevskaya Vladislava V, Pavlov Dmitry I, Kovrizhina Anastasia R, Sukhikh Taisiya S, Sadykov Evgeniy H, Dorovatovskii Pavel V, Lazarenko Vladimir A, Khlebnikov Andrei I, Potapov Andrei S

机构信息

Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia.

Kizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin Ave., 634050 Tomsk, Russia.

出版信息

Pharmaceutics. 2023 Jun 23;15(7):1802. doi: 10.3390/pharmaceutics15071802.

11-Indeno[1,2-]quinoxalin-11-one oxime () 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 (- or -) 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, adopts the -configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed -configuration that could be stabilized only by an intramolecular hydrogen bond.