Some 2, 3, 6-trisubstituted quinoxaline derivatives were synthesized and their antispasmodic activities were determined on the isolated rat ileum. In the synthesis, some dicarbonyl compounds were reacted with substituted or non-substituted o-phenylenediamines in the presence of acetic acid and gained eighteen compounds. All spectral and elemental analyses of the compounds complete and their structures were elucidated. The pharmacological experiments indicate that the compounds 12,13,18 were most active derivatives and their LD50 values were found to be greater than 100 mg/kg (i.p.).
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Biochem Biophys Res Commun
February 2013
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
GDK-100017, a 2,3,6-trisubstituted quinoxaline derivative, reduced β-catenin-T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity and inhibited cell proliferation in a dose-dependent manner with an IC₅₀ value of about 10 μM in A549/Wnt2 cells. GDK-100017 down-regulated the expression of Wnt/β-catenin pathway target genes such as cyclin D1 and Dkk1 but not c-myc or survivin. GDK-100017 inhibited cell proliferation by arresting the cell cycle in the G1 phase not only in A549/wnt2 cells but also in SW480 colon cancer cells.
View Article and Find Full Text PDFBioorg Med Chem
September 2011
Center for Innovative Drug Library Research, Dongguk University, Pil-dong 3-ga, Jung-gu, Seoul 100-715, Republic of Korea.
We developed Wnt/β-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b]pyrazine core skeletons showed were shown to higher activity than 2,3,6-trisubstituted quinoxaline's and thus hold promise for use as potential small-molecule inhibitors of the Wnt/β-catenin signal pathway in non-small-cell lung cancer cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound 954, which presented the highest activity with a fit value of 2.
View Article and Find Full Text PDFBioorg Med Chem Lett
October 2010
Graduate School of Biotechnology, Korea University, Seoul 136701, Republic of Korea.
We screened 1434 small heterocyclic molecules and identified thirteen 2,3,6-trisubstituted quinoxaline derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cell proliferation. In the screen, some of the hit compounds such as the ethylene group-coupled quinoxaline derivatives were shown to hold promise for use as potential small-molecule inhibitors of the Wnt/β-catenin signal pathway in non-small-cell lung cancer cell lines.
View Article and Find Full Text PDFBoll Chim Farm
March 1996
Department of Pharmaceutical Chemistry Faculty of Pharmacy, Anadolu University Eskisehir, Turkey.
Some 2, 3, 6-trisubstituted quinoxaline derivatives were synthesized and their antispasmodic activities were determined on the isolated rat ileum. In the synthesis, some dicarbonyl compounds were reacted with substituted or non-substituted o-phenylenediamines in the presence of acetic acid and gained eighteen compounds. All spectral and elemental analyses of the compounds complete and their structures were elucidated.
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