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Upstream product

• 82173-01-1 N-(2-Fluorophenyl)-1H-imidazol-2-carboxamide 
• 23309-16-2 1-(2-nitrophenyl)-1H-imidazole 
• 88-73-3 2-Chloronitrobenzene 
• 1454816-05-7 N-(2-iodophenyl)-1H-imidazole-2-carboxamide 
• 2213-63-0 2,3-dichloroquinoxaline 
• 191349-68-5 2-chloro-3-(2,2-dimethoxyethylamino)quinoxaline 
• 26286-54-4 1-(2-aminophenyl)imidazole 
• 530-62-1 1,1'-carbonyldiimidazole 

Relevant academic research and scientific papers

Imidazo[1,2-a]quinoxalines derivatives grafted with amino acids: Synthesis and evaluation on A375 melanoma cells

Imiqualines (imidazoquinoxaline derivatives) are anticancer compounds with high cytotoxic activities on melanoma cell lines. The first generation of imiqualines, with two lead compounds (EAPB0203 and EAPB0503), shows remarkable in vitro (IC50 = 1 570 nM and IC50 = 200 nM, respectively, on the A375 melanoma cell line) and in vivo activity on melanoma xenografts. The second generation derivatives, EAPB02302 and EAPB02303, are more active, with IC50 = 60 nM and IC50 = 10 nM, respectively, on A375 melanoma cell line. The aim of this study was to optimize the bioavailability of imiqualine derivatives, without losing their intrinsic activity. For that, we achieved chemical modulation on the second generation of imiqualines by conjugating amino acids on position 4. A new series of twenty-five compounds was efficiently synthesized by using microwave assistance and tested for its activity on the A375 cell line. In the new series, compounds 11a, 9d and 11b show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC50 = 403 nM, IC50 = 128 nM and IC50 = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability.

Imidazo[1,2-a]quinoxalines for melanoma treatment with original mechanism of action

The malignant transformation of melanocytes causes several thousand deaths each year, making melanoma an important public health concern. Melanoma is the most aggressive skin cancer, which incidence has regularly increased over the past decades. We described here the preparation of new compounds based on the 1-(3,4-dihydroxyphenyl)imidazo[1,2-a]quinoxaline structure. Different positions of the quinoxaline moiety were screened to introduce novel substituents in order to study their influence on the biological activity. Several alkylamino or alkyloxy groups were also considered to replace the methylamine of our first generation of Imiqualines. Imidazo[1,2-a]pyrazine derivatives were also designed as potential minimal structure. The investigation on A375 melanoma cells displayed interesting in vitro low nanomolar cytotoxic activity. Among them, 9d (EAPB02303) is particularly remarkable since it is 20 times more potent than vemurafenib, the reference clinical therapy used on BRAF mutant melanoma. Contrary to the first generation, EAPB02303 does not inhibit tubulin polymerization, as confirmed by an in vitro assay and a molecular modelisation study. The mechanism of action for EAPB02303 highlighted by a transcriptomic analysis is clearly different from a panel of 12 well-known anticancer drugs. In vivo EAPB02303 treatment reduced tumor size and weight of the A375 human melanoma xenografts in a dose-dependent manner, correlated with a low mitotic index but not with necrosis.

Substantial Cellular Penetration of Fluorescent Imidazoquinoxalines

Fluorescent tools have revolutionized our capability to visualize, probe, study, and understand the biological cellular properties, processes and dynamics, enabling researchers to improve their knowledge for example in cancer field. In this paper, we use the peculiar properties of our Imiqualines derivatives to study their cellular penetration and distribution in a human melanoma cell line A375 using confocal microscopy. Preliminary results on colocalization with the potent protein target c-Kit of our lead are also described.

Optimization of Drug Candidates That Inhibit the D-Loop Activity of RAD51

RAD51 is the central protein in homologous recombination (HR) repair, where it first binds ssDNA and then catalyzes strand invasion via a D-loop intermediate. Additionally, RAD51 plays a role in faithful DNA replication by protecting stalled replication forks; this requires RAD51 to bind DNA but may not require the strand invasion activity of RAD51. We previously described a small-molecule inhibitor of RAD51 named RI(dl)-2 (RAD51 inhibitor of D-loop formation #2, hereafter called 2 h), which inhibits D-loop activity while sparing ssDNA binding. However, 2 h is limited in its ability to inhibit HR in vivo, preventing only about 50 % of total HR events in cells. We sought to improve upon this by performing a structure–activity relationship (SAR) campaign for more potent analogues of 2 h. Most compounds were prepared from 1-(2-aminophenyl)pyrroles by forming the quinoxaline moiety either by condensation with aldehydes, then dehydrogenation of the resulting 4,5-dihydro intermediates, or by condensation with N,N′-carbonyldiimidazole, chlorination, and installation of the 4-substituent through Suzuki–Miyaura coupling. Many analogues exhibited enhanced activity against human RAD51, but in several of these compounds the increased inhibition was due to the introduction of dsDNA intercalation activity. We developed a sensitive assay to measure dsDNA intercalation, and identified two analogues of 2 h that promote complete HR inhibition in cells while exerting minimal intercalation activity.

Fluorescence Study of Imidazoquinoxalines

The fluorescence properties of eleven novel derivatives based on the imidazo[1,2-a]quinoxaline structures have been studied. The absorption and emission spectra of these compounds have been recorded in dimethylsulfoxide solution. The phenyl substituting group on position 1 gives them particular properties thanks to the diverse hydroxy or methoxy decorating moieties, especially when they are multiplied or mixed. The investigated fluorescence auto-quenching revealed that the decreasing fluorescence intensity correlated only with the chemical structures of the aromatic compounds.

A recyclable Cu-catalyzed C-N coupling reaction in water and its application to synthesis of imidazo[1,2-a]quinoxaline

Polystyrene-supported pyrrole-2-carbohydrazide (PSP) was synthesized and combined with CuI to make up a recyclable heterogeneous catalytic system for Ullmann-type C-N coupling reaction in water. In which, a variety of functionalized aryl halides animated efficiently with anilines, benzylamine, aliphatic amines, and imidazole. its preliminary application resulted in a more practical synthesis of imidazo[1,2-a]quinoxaline.

IMIDAZOL[1,2-alpha]QUINOXALINES AND DERIVATIVES FOR THE TREATMENT OF CANCERS

Imidazo[1,2-a]quinoxaline compounds for the treatment of cancers as well as pharmaceutical compositions that include these compounds and their uses in therapy. The compound of general formula (I):

New imidazo[1,2-a]quinoxaline derivatives: Synthesis and in vitro activity against human melanoma

New imidazo[1,2-a]quinoxaline analogues have been synthesized in good yields via a bimolecular condensation of 2-imidazole carboxylic acid, followed by a coupling with ortho-fluoroaniline and subsequent substitution on the imidazole ring by Suzuki Cross-c

Imidazo[1,2-a]quinoxalin-4-amines active as adenosine antagonists, process for their preparation and pharmaceutical compositions thereof

PCT No. PCT/IB96/01291 Sec. 371 Date May 12, 1998 Sec. 102(e) Date May 12, 1998 PCT Filed Nov. 22, 1996 PCT Pub. No. WO97/19079 PCT Pub. Date May 29, 1997Imidazo[1,2-a]quinoxalin-4-amines derivatives of formula (I) are described, and salt thereof active as adenosine antagonists and a process for their preparation and pharmaceutical compositions containing them as therapeutically active compounds for psychiatric and neurological disorders of the central nervous system.

Imidazo[1,2-a]quinoxalin-4-amines: A novel class of nonxanthine A1- adenosine receptor antagonists

The syntheses and A1 adenosine receptor affinities of a number of imidazo[1,2-a]quinoxalin-4-amines are reported. Structure-activity relationships within the series and in comparison with other similar tricyclic nonxanthine adenosine antagonists are discussed, leading to a putative common binding mode of these nitrogen-containing heterocycles to A1 adenosine receptors. Secondary amino compounds displayed the best affinities toward A1 receptors, while the tertiary amines were almost devoid of activity, thus suggesting a crucial role for the hydrogen bond-forming 4-NH group. Remarkably higher potencies for 1-methyl and N-cyclopentyl derivatives were also found. 4-Cyclopentylamino-1-methylimidazo[1,2-a]quinoxaline (IRFI 165) is the most potent compound in this series, having K(i)(A1) = 7.9 nM. It is also provided with a good A1 selectivity both versus A(2a) and A3 subtypes and was selected for further pharmacological studies.