The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS.

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Cao X, You QD, Li ZY, Liu XR, Xu D, Guo QL, Shang J, Chern JW, Chen ML

The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS.

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6206-9. doi: 10.1016/j.bmcl.2008.10.006. Epub 2008 Oct 5.

PubMed ID

18930653 [ 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-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents 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 inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC(50) values of 34.8 nM and 26.7 microM. Several compounds also showed moderate anti-proliferation at 10 microM against colon and liver cancer 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
Bosutinib	Proto-oncogene tyrosine-protein kinase Src	IC 50 (nM)	1.8	N/A	N/A	Details