Design and synthesis of 7-alkoxy-4-heteroarylamino-3-quinolinecarbonitriles as dual inhibitors of c-Src kinase and nitric oxide synthase.

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Cao X, You QD, Li ZY, Guo QL, Shang J, Yan M, Chern JW, Chen ML

Design and synthesis of 7-alkoxy-4-heteroarylamino-3-quinolinecarbonitriles as dual inhibitors of c-Src kinase and nitric oxide synthase.

Bioorg Med Chem. 2008 Jun 1;16(11):5890-8. doi: 10.1016/j.bmc.2008.04.065. Epub 2008 Apr 29.

PubMed ID

18485715 [ View in PubMed

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Abstract

Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC(50) values of 6.58 and 7.61microM toward colon cancer HT-29 and liver cancer HepG2 cell lines.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Bosutinib	Proto-oncogene tyrosine-protein kinase Src	IC 50 (nM)	1.2	N/A	N/A	Details