A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/beta-catenin pathway inhibitors in non-small-cell lung cancer cell lines

作者：Gong Young Dae^*; Dong Mi Sook; Lee Sang Bum; Kim Nayeon; Bae Mi Seon; Kang Nam Sook

来源：Bioorganic & Medicinal Chemistry, 2011, 19(18): 5639-5647.

DOI：10.1016/j.bmc.2011.07.028

• Wnt2
• beta-Catenin
• Pyrido[ 2,3,-b]pyrazines
• Inhibitors
• Anti-cancer
• Pharmacophore

We developed Wnt/beta-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b] pyrazine derivatives that were able to inhibit the Wnt/b-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/beta-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 2.81. The pharmacophore mapping for the compounds including 954, pyrido[2,3,-b] pyrazine core had hydrogen-bond acceptor site and hydrophobic center roles.

• 出版日期2011-9-15