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

被引：3

作者：

Matveevskaya, Vladislava V. V. ^{[1
]}

Pavlov, Dmitry I. I. ^{[1
]}

Kovrizhina, Anastasia R. R. ^{[2
]}

Sukhikh, Taisiya S. S. ^{[1
]}

Sadykov, Evgeniy H. H. ^{[1
]}

Dorovatovskii, Pavel V. V. ^{[3
]}

Lazarenko, Vladimir A. A. ^{[3
]}

Khlebnikov, Andrei I. I. ^{[2
]}

Potapov, Andrei S. S. ^{[1
]}

机构：

[1] Russian Acad Sci, Nikolaev Inst Inorgan Chem, Siberian Branch, 3 Lavrentiev Ave, Novosibirsk 630090, Russia

[2] Natl Res Tomsk Polytech Univ, Kizhner Res Ctr, 30 Lenin Ave, Tomsk 634050, Russia

[3] Natl Res Ctr Kurchatov Inst, Kurchatov Sq 1, Moscow 123182, Russia

来源：

PHARMACEUTICS | 2023年 / 15卷 / 07期

关键词：

kinase inhibitor; oxime; crystal structure; nuclear magnetic resonance; rotation barrier; DENSITY-FUNCTIONAL METHODS; MOLECULAR-ORBITAL METHODS; BASIS-SETS; CHEMICAL-SHIFTS; ADJUSTABLE-PARAMETERS; C-13; H-1; DERIVATIVES; ASSIGNMENT; INTEGRATION;

D O I：

10.3390/pharmaceutics15071802

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：20

共 22 条

[1] Synthesis, biological evaluation, and molecular modeling of 11H-indeno[1,2-b]quinoxalin-11-one derivatives and tryptanthrin-6-oxime as c-Jun N-terminal kinase inhibitors
Schepetkin, Igor A.
Khlebnikov, Andrei I.
Potapov, Andrei S.
Kovrizhina, Anastasia R.
Matveevskaya, Vladislava V.
Belyanin, Maxim L.
Atochin, Dmitriy N.
Zanoza, Svitlana O.
Gaidarzhy, Nadiya M.
Lyakhov, Sergiy A.
Kirpotina, Liliya N.
Quinn, Mark T.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 161 : 179 - 191
[2] Novel c-Jun N-Terminal Kinase (JNK) Inhibitors with an 11H-Indeno[1,2-b]quinoxalin-11-one Scaffold
Liakhov, Serhii A.
Schepetkin, Igor A.
Karpenko, Olexander S.
Duma, Hanna, I
Haidarzhy, Nadiia M.
Kirpotina, Liliya N.
Kovrizhina, Anastasia R.
Khlebnikov, Andrei, I
Bagryanskaya, Irina Y.
Quinn, Mark T.
MOLECULES, 2021, 26 (18):
[3] 11H-Indeno[1,2-b]quinoxalin-11-one
Ghalib, Raza Murad
Hashim, Rokiah
Sulaiman, Othman
Hemamalini, Madhukar
Fun, Hoong-Kun
ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 2010, 66 : O1494 - U2123
[4] Arene-Ruthenium(II) Complexes Containing 11H-Indeno[1,2-b]quinoxalin-11-one Derivatives and Tryptanthrin-6-oxime: Synthesis, Characterization, Cytotoxicity, and Catalytic Transfer Hydrogenation of Aryl Ketones
Matveevskaya, Vladislava V.
Pavlov, Dmitry, I
Sukhikh, Taisiya S.
Gushchin, Artem L.
Ivanov, Alexander Yu
Tennikova, Tatiana B.
Sharoyko, Vladimir V.
Baykov, Sergey, V
Benassi, Enrico
Potapov, Andrei S.
ACS OMEGA, 2020, 5 (19): : 11167 - 11179
[5] Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy
Andrianov, Viacheslav V.
Schepetkin, Igor A.
Bazan, Leah V.
Gainutdinov, Khalil L.
Kovrizhina, Anastasia R.
Atochin, Dmitriy N.
Khlebnikov, Andrei I.
MOLECULES, 2024, 29 (16):
[6] QUINOXALINE .4. REACTION OF ALDEHYDES WITH 11H-INDENO(1,2-B)QUINOXALINE AND CONDENSATION OF 11H-INDENO(1,2-B)QUINOXALIN-11-ONE WITH AROMATIC AMINES
LIPPMANN, E
STOLPMAN.HG
ZEITSCHRIFT FUR CHEMIE, 1971, 11 (04): : 150 - &
[7] 11H-Indeno[1,2-b]quinoxalin-11-one 2-(4-ethylbenzylidene)hydrazone
Kovrizhina, Anastasia R.
Samorodova, Elizaveta I.
Khlebnikov, Andrei I.
MOLBANK, 2021, 2021 (04)
[8] Iridium(III) and Rhodium(III) Half-Sandwich Coordination Compounds with 11H-Indeno[1,2-b]quinoxalin-11-one Oxime: A Case of Spontaneous Resolution of Rh(III) Complex
Matveevskaya, Vladislava V.
Pavlov, Dmitry, I
Potapov, Andrei S.
INORGANICS, 2022, 10 (11)
[9] SYNTHESIS OF 11H-INDENO[1,2-B]QUINOXALIN-11-ONE AZINES CONTAINING 4-SUBSTITUTED-PHENYL-3-THIAZOLIN-2-ONE MOIETY
RAO, VR
KUMAR, RA
RAO, TVP
INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, 1984, 23 (06): : 563 - 564
[10] Synthesis, Characterization and Superoxide Dismutase-like Activity of Novel Cu(II), Ni(II), Co(II), and Zn(II) Complexes with 11H-Indeno[1,2-b]quinoxalin-11-one Oxime Ligand.
Khlebnikov, A. I.
Schepetkin, I. A.
Chernova, N. P.
Anosova, G. A.
Potapov, A. S.
Atochin, D.
MOLECULAR BIOLOGY OF THE CELL, 2017, 28

← 1 2 3 →