Crystal structure, Hirshfeld surface analysis and density functional theory study of 1-nonyl-3-phenylquinoxalin-2-one

In the title molecule, C23H28N2O, the phenyl ring is inclined to the quinoxaline ring system at a dihedral angle of 20.40 (9)°. In the crystal, C—H...O interactions between neighbouring molecules form chains along the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (70.6%), H...C/C...H (15.5%) and H...O/O...H (4.6%) interactions. The optimized structure calculated using density functional theory at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap is 3.8904 eV. Part of the n-nonyl chain attached to one of the nitrogen atoms of the quinoxaline ring system shows disorder and was refined with a double conformation with occupancies of 0.604 (11) and 0.396 (11).

Quinoxaline Moiety: A Potential Scaffold against Mycobacterium tuberculosis

Background. The past decades have seen numerous efforts to develop new antitubercular agents. Currently, the available regimens are lengthy, only partially effective, and associated with high rates of adverse events. The challenge is therefore to develop new agents with faster and more efficient action. The versatile quinoxaline ring possesses a broad spectrum of pharmacological activities, ensuring considerable attention to it in the field of medicinal chemistry. Objectives. In continuation of our program on the pharmacological activity of quinoxaline derivatives, this review focuses on potential antimycobacterial activity of recent quinoxaline derivatives and discusses their structure–activity relationship for designing new analogs with improved activity. Methods. The review compiles recent studies published between January 2011 and April 2021. Results. The final total of 23 studies were examined. Conclusions. Data from studies of quinoxaline and quinoxaline 1,4-di-N-oxide derivatives highlight that specific derivatives show encouraging perspectives in the treatment of Mycobacterium tuberculosis and the recent growing interest for these scaffolds. These interesting results warrant further investigation, which may allow identification of novel antitubercular candidates based on this scaffold.

2-Phenoxy-3-trichloromethylquinoxalines Are Antiplasmodial Derivatives with Activity against the Apicoplast of Plasmodium falciparum

The malaria parasite harbors a relict plastid called the apicoplast. Although not photosynthetic, the apicoplast retains unusual, non-mammalian metabolic pathways that are essential to the parasite, opening up a new perspective for the development of novel antimalarials which display a new mechanism of action. Based on the previous antiplasmodial hit-molecules identified in the 2-trichloromethylquinoxaline series, we report herein a structure–activity relationship (SAR) study at position two of the quinoxaline ring by synthesizing 20 new compounds. The biological evaluation highlighted a hit compound (3i) with a potent PfK1 EC50 value of 0.2 µM and a HepG2 CC50 value of 32 µM (Selectivity index = 160). Nitro-containing (3i) was not genotoxic, both in the Ames test and in vitro comet assay. Activity cliffs were observed when the 2-CCl3 group was replaced, showing that it played a key role in the antiplasmodial activity. Investigation of the mechanism of action showed that 3i presents a drug response by targeting the apicoplast and a quick-killing mechanism acting on another target site.

7,8-Dimethyl-11H-indeno[1,2-b]quinoxalin-11-one

In the title compound, C17H12N2O, the mean planes of the indene ring and quinoxaline system (r.m.s. deviations = 0.0131 and 0.0082 Å) are approximately parallel to one another, making a dihedral angle of 1.2 (5)°. This means that the indeno[1,2-b]quinoxaline ring is almost in the same plane (r.m.s. deviation = 0.0181 Å).

Recent advancement in the synthesis of diverse spiro-indeno[1,2-b]quinoxalines: a review

The nitrogen-containing indeno[1,2-b]quinoxaline ring is a privileged structurally fused active system and has notable applications in various fields of chemistry.

11,11-Diphenyl-11H-indeno[1,2-b]quinoxaline

In the title compound, C27H18N2, the mean planes of the pendant benzene rings are approximately perpendicular to one another, making a dihedral angle of 79.3 (5)°; the indeno[1,2-b]quinoxaline ring system (r.m.s. deviation = 0.1197 Å) is twisted with respect to the pendant benzene rings by 70.0 (4) and 67.6 (3)°. Weak aromatic π–π stacking [centroid–centroid separation = 3.628 (2) Å] and C—H...π interactions occur in the crystal.

Convenient Synthesis of New Heterocycles Containing the Quinoxaline Ring System

: The aim of the current article was to describe simple procedures for the synthesis of new heterocycles incorporating the quinoxaline moiety using benzene-1,2-diamine and quinoxaline-2,3- dithiol as precursors. Simple synthetic methods are described for the synthesis of new heterocycles using commercially available chemicals. Also, the new compounds were determined using analytical and spectroscopic methods including single X-ray crystal structures. A series of new heterocycles containing the quinoxaline nucleus have been synthesized in good yields using simple and convenient procedures. A process has been described for the synthesis of new heterocycles containing the quinoxaline moiety that might be difficult to synthesize by other routes.

Ethyl 6′-cyano-7′-phenyl-1′,6′,7′,7a'-tetrahydro-3′H-spiro[indeno[1,2-b]quinoxaline-11,5′-pyrrolo[1,2-c]thiazole-6′-carboxylate

In the title compound, C22H22ClN4O2S, the angle between the mean planes of the indene ring and the quinoxaline ring system is 3.93 (11)°. The five-membered indene and thiazole rings both adopt envelope conformations while the pyrrole ring adopts a twisted conformation. The two acceptor O atoms form a chelated three-centred hydrogen bond with a phenyl C atom.

Ethyl 2-[(3-methylquinoxalin-2-yl)sulfanyl]acetate

In the title molecule, C13H14N2O2S, the dihedral angle between the pyrazine and benzene ring planes is 2.21 (5)°. The mean plane of the quinoxaline ring system is inclined to the sufanylacetate substituent by 81.74 (2)°. In the crystal, inversion-related C—H...N hydrogen bonds form dimers, which are linked into oblique stacks along thea-axis direction by C—H...O hydrogen bonds and π–π-stacking interactions.

2,3-Bis(benzylthio)-6-methylquinoxaline

In the title compound, C23H20N2S2, the mean planes of the phenyl rings are twisted with respect to the mean plane of the quinoxaline ring system by 73.8 (8) and 72.2 (8)°. A weak intramolecular C—H...N interactions is observed. The methyl group attached to the quinoxaline ring system is disordered over two sets of sites on the benzene ring having occupancies 0.531 (7) and 0.469 (7), respectively. One of the phenyl rings is disordered over two sets of sites having occupancies 0.649 (7) and 0.351 (10), respectively. In the crystal, π–π stacking interactions occur.