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
11<i>H</i>-Indeno[1,2-<i>b</i>]quinoxalin-11-one oxime (<b>IQ-1</b>) 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 configur...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1802 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Vladislava V. Matveevskaya |
| collection | DOAJ |
| description | 11<i>H</i>-Indeno[1,2-<i>b</i>]quinoxalin-11-one oxime (<b>IQ-1</b>) 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 (<i>E</i>- or <i>Z</i>-) 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, <b>IQ-1</b> adopts the <i>E</i>-configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed <i>Z</i>-configuration that could be stabilized only by an intramolecular hydrogen bond. |
| first_indexed | 2024-03-11T00:44:55Z |
| format | Article |
| id | doaj.art-784a6dccd29641498c2f0986e8156355 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:44:55Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-784a6dccd29641498c2f0986e81563552023-11-18T20:54:03ZengMDPI AGPharmaceutics1999-49232023-06-01157180210.3390/pharmaceutics15071802Experimental 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-oximeVladislava V. Matveevskaya0Dmitry I. Pavlov1Anastasia R. Kovrizhina2Taisiya S. Sukhikh3Evgeniy H. Sadykov4Pavel V. Dorovatovskii5Vladimir A. Lazarenko6Andrei I. Khlebnikov7Andrei S. Potapov8Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, RussiaNikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, RussiaKizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin Ave., 634050 Tomsk, RussiaNikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, RussiaNikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, RussiaNational Research Centre “Kurchatov Institute”, Kurchatov Square 1, 123182 Moscow, RussiaNational Research Centre “Kurchatov Institute”, Kurchatov Square 1, 123182 Moscow, RussiaKizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin Ave., 634050 Tomsk, RussiaNikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Ave., 630090 Novosibirsk, Russia11<i>H</i>-Indeno[1,2-<i>b</i>]quinoxalin-11-one oxime (<b>IQ-1</b>) 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 (<i>E</i>- or <i>Z</i>-) 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, <b>IQ-1</b> adopts the <i>E</i>-configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed <i>Z</i>-configuration that could be stabilized only by an intramolecular hydrogen bond.https://www.mdpi.com/1999-4923/15/7/1802kinase inhibitoroximecrystal structurenuclear magnetic resonancerotation barrier |
| spellingShingle | 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 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 Pharmaceutics kinase inhibitor oxime crystal structure nuclear magnetic resonance rotation barrier |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | kinase inhibitor oxime crystal structure nuclear magnetic resonance rotation barrier |
| url | https://www.mdpi.com/1999-4923/15/7/1802 |
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