Pyrrolo (1,2-a) quinoxalines (author's transl)

Pyrrolo [1,2-a] quinoxalines 2-Ethoxy-3-acetoacetylquinoxaline (1) reacts with ethylorthoformate/acetic anhydride forming 2-acetyl-1,4-diethoxy-3-hydroxy-pyrrolo [1,2-a] quinoxaline 4a .     

Synthesis of Pyrrolo[1,2-a]quinoxalines via gold(I)-mediated cascade reactions

In this study, we developed an efficient tandem process of hydroamination and hydroarylation using a gold catalyst to enable and study the reactions between pyrrole-substituted anilines and alkynes. The gold(I)-catalyzed reactions were achieved in toluene at 80 °C over a reaction time of 1?6 h. These reactions are applicable to a variety of aromatic amino compounds and both the terminal and internal alkynes. Substituted pyrrolo[1,2-a]quinoxalines were obtained in moderate to excellent yields. A presumed mechanism involving intermolecular C?N bond formation and intramolecular nucleophilic reaction via a cationic gold complex has been proposed on the basis of the deuterium labeling studies.     

Substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones

The synthesis of a series of substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones is described. Several members of the series exhibit enhanced antiallergic and bronchodilator activity and reduced side effects as compared to theophylline. Structure-activity relationships and metabolic considerations are discussed for the series. Analogues substituted with a 4-(4-chlorobenzyl) moiety, such as 33 and 40, shown an optimal balance of antiallergic and bronchodilator activity and are of particular interest. Compound 33 is significantly more potent than theophylline against both metacholine- and antigen-induced bronchospasms, does not affect spontaneous motor activity, and shows minimal cardiovascular effects in the rat.     

Synthesis and Antiaggregant Activity of 3-(2-Aryl-2-oxoethyl)-3-methoxy-2-oxo-2,3-dihydroimidazo[1,2-a]pyridine Hydrochlorides

Pharmaceutical Chemistry Journal -     

Synthesis, antimalarial activity, and molecular modeling of new pyrrolo[1,2-a]quinoxalines, bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines

Three pyrrolo[1,2-a]quinoxalines, 15 bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines were synthesized from various substituted nitroanilines or nitropyridines and tested for their in vitro activity upon the erythrocytic development of Plasmodium falciparum strains with different chloroquine-resistance status. Bispyrrolo[1,2-a]quinoxalines showed superior antimalarial activity with respect to monopyrrolo[1,2-a]quinoxalines. The best activity was observed with bispyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that the presence of a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus increased the pharmacological activity. Drug effects upon beta-hematin formation were assayed and showed similar or higher inhibitory activities than CQ. A possible mechanism of interaction implicating binding of pyrroloquinoxalines to beta-hematin was supported by molecular modeling.     

Synthesis and antimicrobial activity of new substituted 10-methyl-1,2-dihydro-1-oxo-1,2,4-triazino(4,5-a)indoles

Ten new 4,8-disubstituted 10-methyl-1,2-dihydro-1-oxo-1,2,4-triazino(4,5-a)indoles (5 and 6) were prepared by refluxing various 5-substituted indole-2-carbohydrazides (4) with triethylorthoformate or triethylorthoacetate in dimethylformamide. These derivatives were evaluated for their antimicrobial activity. Some of the title compounds possess fairly potent antimicrobial activity.     

Synthesis of novel 4,5-dihydropyrrolo[1,2-a]quinoxalines,pyrrolo[1,2-a]quinoxalin]-2-ones and their antituberculosis and anticancer activity

A facile strategy was developed for the synthesis of biologically important 4,5-dihydropyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin]-2-ones by treating 2-(1H-pyrrol-1-yl)anilines with imidazo[1,2-a]pyridine-3-carbaldehyde or isatin, using amidosulfonic acid (NH₃SO₃) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity. The compounds were evaluated for their antituberculosis, antibacterial, and anticancer activities. It is worth noting that compounds 3d and 3e demonstrated a minimum inhibitory concentration value of 6.25 µM against Mycobacterium tuberculosis H37Rv, whereas compounds 3d , 3g , 5d , 5e , and 5i showed a remarkable inhibition of A549, DU145, HeLa, HepG2, MCF-7, and B16-F10 cell lines, respectively. Staphylococcus aureus was inhibited by compounds 5b , 5e , 5d , 5g , and 5l at 32 µg/ml.     

Synthesis and antiinflammatory and analgesic activity of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids. The 6-substituted compounds

5-Aroyl-6-substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carbo xylic acids were synthesized and assayed for analgesic and antiinflammatory activity. Several of these compounds, notably the 5-(4-fluoro- and 4-chlorobenzoyl)-6-methyl derivatives 25 and 26 and the 5-(4-methyl-, 4-fluoro-, 4-chloro-, and 4-methoxybenzoyl)-6-chloro congeners 31-34 were of equal or greater potency than indomethacin as antiinflammatory and analgesic agents both in acute and chronic animal models.     

Synthesis and antiinflammatory and analgesic activity of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and related compounds

5-Acyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and the homologous pyridine and azepine derivatives were synthesized and assayed for antiinflammatory and analgesic activity. 5-Benzoyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acid and the corresponding p-methoxy compound 74 were selected for evaluation as analgesic agents in humans on the basis of their high potency in the mouse phenylquinone writhing assay as well as on their minimal liability to elicit gastrointestinal erosion in rats on chronic administration. Extensive quantitative structure-activity relationship (QSAR) studies of the benzoylpyrrolopyrrolecarboxylic acids have demonstrated that the analgesic (mouse writhing) and antiinflammatory (rat carrageenan paw) potencies of these compounds are satisfactorily correlated with the steric and hydrogen-bonding properties of the benzoyl substituent(s). The 4-vinylbenzoyl compound 95, which was correctly predicted to be highly active in both assays on this basis, is undergoing advanced pharmacological evaluation in animals as a potential antiinflammatory agent.     

Synthesis of new derivatives of 1-alkyl-2-aryl-1H-2,3-dihydroimidazo[1,2-a]pyrimidin-5-one active in CNS. Part 2. Synthesis and results of preliminary pharmacological screening of 7-(substituted)amino-1-alkyl-2-aryl-1H-2,3-dihydroimidazo[1,2-a]pyrimid in-5- ones

Synthesis of new 7-(substituted)amino-1-alkyl-2-aryl-1H-2,3-dihydroimidazo[1,2-a]py rimidin-5- ones bearing the 4-arylpiperazin-1-yl moiety connected by ethyl or acetoyl two-carbonyl chain extension was described. The arylpiperazinyl moiety was introduced by alkylation or acylation with corresponding halogeno-derivatives. Preliminary pharmacological screening showed the 7-(substituted)-amino derivatives of the system investigated to exhibit the CNS activity lesser than that of the 7-amino derivatives and to have no effect on the serotonin neurotransmission pathway.